Citation: Tianyuan Xu, Shanming Ji, Chunhua Jin, Ming Mei, Jingxue Yin. EARLY AND LATE STAGE PROFILES FOR A CHEMOTAXIS MODEL WITH DENSITY-DEPENDENT JUMP PROBABILITY[J]. Mathematical Biosciences and Engineering, 2018, 15(6): 1345-1385. doi: 10.3934/mbe.2018062
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The motion of cells moving towards the higher concentration of a chemical signal is called chemotaxis. For example, bacteria moves toward the highest concentration of food molecules to find food. A well-known chemotaxis model was initially proposed by Keller and Segel [15] in 1971, subsequently, a number of variations of the Keller-Segel system were proposed and have been extensively studied during the past four decades, for example, see the survey papers [1,12] and the references therein. Especially, chemotaxis models also appear in medical mathematics. Many factors effect the migration mechanisms of tumour cells. For example, the extracellular matrix (ECM), to which the tumour cell to be attached, inhibits the cell polarizes and elongates to migrate. ECM-degrading enzymes (MDE) cleave ECM fibers into smaller chemotactic fragments to facilitate cell-migration [6]. In [4], Chaplain and Anderson introduced a model for tumour invasion mechanism, which describes tumour invasion phenomenon in accounting for the role of chemotactic ECM fragments named ECM*, produced by a biological reaction between ECM and MDE. In these models, the tumour cell random motility is assumed to be a constant, which leads to linear isotropic diffusion. However, in realistic situation, it is emphasized that migration of the tumour cells through the ECM fibers should rather be regarded like movement in a porous medium with degenerate diffusion from a physical point of view [38]. Compared with the classical tumour invasion model with linear diffusion, the mathematical analysis of the nonlinear diffusion system has to cope with considerable additional challenges and is much less understood. Several chemotaxis models with nonlinear diffusion have been recently proposed and analyzed, e.g. [18,38,45,46], where the nonlinear diffusions in these studies were still assumed to be non-degenerate. For tumour angiogenesis model and relevant mathematical analysis with or without degenerate diffusion, we refer to [14,22,23,48,49,50,52,54] and the references therein.
Tumour cells can modify their migration mechanisms in response to different conditions [6]. There are two potentially important factors: (ⅰ) the effect of cell-density on the probability of cell movement; (ⅱ) the effect of signal-mediated cell-density sensing mechanisms on movement [28]. For interacting cell population, Painter and Sherratt [29] further presented four different sensing strategies: strictly local, neighbour based, local average and gradient. Cell movement involves the processing of multiple signals, each of them may act on the cells in different ways. For neighbor-based and gradient-based rules, Painter and Hillen [28] proposed volume filling approach, that is, the movement of cells is inhibited by the neighboring site where the cells are densely packed. Inspired by the idea of Painter et al. [28,29] and recently in Xu et al. [57], we extend Chaplain and Anderson's model [4] to a new one with density-dependent jump probability of tumour cells as follows, which is concerned with the competition between the following several biological mechanisms: degenerate diffusion, density-dependent chemotaxis, and general logistic growth. That is,
{∂u∂t=∇⋅(q(u)∇u)−∇⋅(q(u)u∇v)+μuδ(1−ru),x∈Ω,t>0,∂v∂t=Δv+wz,x∈Ω,t>0,∂w∂t=−wz,x∈Ω,t>0,∂z∂t=Δz−z+u,x∈Ω,t>0. | (1) |
The detailed derivation of the model (1) will be carried out in the Appendix. Here,
The unbiased cell movement modelled by linear diffusion motility mechanism has been used extensively to study a variety of cell biology problems. However, when cells are close enough for regular contacts, they will inevitably interact [29]. Linear diffusion of each cell type is inappropriate for the close-packed cell populations involved in early tumour growth. The degenerate nonlinear diffusion can represent ''population pressure'' in cell invasion models [29], which arises from the ecology dispersal literature [9,10,24,58]. A high cell density results in increased probability of a cell being ''pushed'' from a site. In this case, large dispersal takes place in highly populated regions, but low mobility occurs in the regions of low cell density. The cell invasions described by nonlinear degenerate systems with the density-dependent nonlinear diffusivity function
Some studies found that degenerate nonlinear diffusion model related to the porous media equation (PME) provides a better match to experimental cell density profiles [34]. Sengers and coworkers [30] developed a set of in vitro cell invasion experiments and image analysis to quantify the migration and proliferation of two different skeletal cell types, including human osteosarcoma MG63 cells and human bone marrow stromal cells (HBMSCs). Comparison of experimental and simulated cell distribution are shown in Fig. 1 in [30], where the cell density considerably increased and simultaneously spread outwards from the centre of the cell circle, producing a new cell migration front every day. Their results show that the MG63 migration with sharp front is best described by a degenerate diffusion model with the diffusivity
An interesting work related to the chemotaxis model mentioned above is [7], in which they considered the following chemotaxis system with linear diffusion
{∂u∂t=Δu−∇⋅(u∇v),x∈Ω,t>0,∂v∂t=Δv+wz,x∈Ω,t>0,∂w∂t=−wz,x∈Ω,t>0,∂z∂t=Δz−z+u,x∈Ω,t>0. | (2) |
It is proved the existence of global solutions and the asymptotic behaviors of global solutions as time goes to infinity by using the properties of the Neumann heat semigroup
Apart from the diffusive motility, another important mechanism in cell invasion is cell proliferation. In [35], an assay using gut organ culture validates that proliferation at the invading front is the critical mechanism driving apparently directed invasion. Cells at the invasive front are proliferative and migrate into previously unoccupied tissue. It also has important implications for carcinoma invasion. Tumour invasion systems with proliferative cells have been studied extensively [8,21,26]. Logistic growth is one of important models of proliferation to a carrying capacity limit [24]. Von Bertalanffy derived a general logistic growth law for avascular tumour growth [44], and suggested that
f(u)=γuλ−δuμ, |
where
Compared to the linear cases, the chemotactic system with degenerate diffusion and chemotactic sensitivity is more complex and challenging. Since the first equation of (1) is degenerate at any point where
In this paper, we provide a more realistic description of cell migration process for early and late stages. It is worth to mention that our stability results of the model (1) give a certain estimate for the speed of the expanding speed of tumour region. We construct suitable subsolutions and supersolutions to show the position of the free boundary for the tumour region. Then, we prove that there exist
A1(t)⊂suppu(⋅,t)⊂¯A2(t)⊂Ω,t∈(0,t0), |
As we all know, for linear diffusion equations with initial data
An in vivo primary tumour initially develops in epithelia and grows within the epithelium before expanding into surrounding tissues [32]. The very early stages of tumour growth are rarely seen clinically due to the small size of the cell masses. However, this early growth has been well studied in vitro using HEPA-1 tumour cells. Small aggregates of several cells formed during the initial hours in culture and accounted for the rapid increase in the mean volume of the cell spheroids. This assay was introduced by Leek [16] in 1999. Then, Owen et al. compared their numerical simulations with this experimental data. There is a good agreement between the experimental and numerical results for the outer spheroid radius [27]. Key results from their study are shown in Fig. 2. Growth was rapid for the initial days, decreased, and approached a horizontal asymptote. It can be difficult to decide what type of model is best suited to a particular biological problem. Different approaches in mathematics can reproduce the same experimental results [3]. Our theoretical results also provide a good fit to the experimental results in [16]. The shape of the growth curve of the cell spheroids is similar to the graph of power function
In contrast with the well known linear cases, the degenerate diffusion is endowed with the interesting feature of slow diffusion, that is, the compact support of solutions propagates at a finite speed. The slow diffusion feature has some advantages and accuracy for describing specified biological processes in the point of view of the physical reality, and it also leads to more challenges in the mathematical studies. For example, in order to investigate the asymptotic behavior of solutions, one must appropriately describe the propagation behavior of its support, which is more likely to be a compact subset of the prescribed domain for some time interval if the initial data are given so. We mention that the Neumann heat semigroup theory and functional transform methods have been proved to be effective in studying the global boundedness and large time behavior for the linear diffusion equations, but they are all inapplicable in the degenerate diffusion case due to the nonlinearity. We establish the global existence of bounded weak solutions to this model by energy estimate technique and methods based on Moser-type iteration. Then we prove that, at the late stage of the tumour migration, the original weak solution time-asymptotically converges to its steady state, even if the initial perturbation is large, namely, the global stability of the steady state. The adopted approach is the technical compactness analysis with the help of the comparison principle deduced by the approximate Hohmgren's approach and two kinds of lower solutions showing the expanding support and the exponentially convergence. The one is a self similar weak lower solution of Barenblatt type and the other kind is an ODE solution.
This paper is organized as follows. In Section 2, we state our main results. We leave the global existence of weak solutions to the corresponding chemotaxis system and their regularity into Section 3 as preliminaries. Section 4 is devoted to the study of compact support property of the tumour cells at early stage and the large time behavior at late stage, showing the exponentially convergence of solutions.
In this section, we first state our main results on the study of expanding compact support of the tumour cells at early stage and the asymptotic behavior at late stage. We leave the detailed derivation on the new chemotaxis model (1) with density-dependent jump probability in the Appendix. We estimate the upper bound and lower bound for expanding speed of tumour cell region at early stage (before the tumour cells spread to the whole body) and show the exponentially convergence of solutions for large time.
We consider the following system (3) with degenerate diffusion
{ut=Δ(q(u)u)−∇⋅(q(u)u∇v)+μuδ(1−u),vt=Δv+wz,wt=−wz,zt=Δz−z+u,x∈Ω,t>0,∂u∂ν=∂v∂ν=∂z∂ν=0,x∈∂Ω,t>0,u(x,0)=u0(x),v(x,0)=v0(x),w(x,0)=w0(x),z(x,0)=z0(x),x∈Ω, | (3) |
where
Since degenerate diffusion equations may not have classical solutions in general, we need to formulate the following definition of generalized solutions for the initial boundary value problem (3).
Definition 2.1. Let
(1)
(2)
(3)
(4)
(5) the identities
∫T0∫Ωuψtdxdt+∫Ωu0(x)ψ(x,0)dx=∫T0∫Ω∇(q(u)u)⋅∇ψdxdt−∫T0∫Ωq(u)u∇v⋅∇ψdxdt−∫T0∫Ωμuδ(1−u)ψdxdt,∫T0∫Ωvtφdxdt+∫T0∫Ω∇v⋅∇φdxdt=∫T0∫Ωwzφdxdt,∫T0∫Ωwtφdxdt=−∫T0∫Ωwzφdxdt,∫T0∫Ωztφdxdt+∫T0∫Ω∇z⋅∇φdxdt=∫T0∫Ω(u−z)φdxdt, |
hold for all
(6)
If
A quadruple
supt∈R+{‖u‖L∞(Ω)+‖v‖W1,∞(Ω)+‖w‖L∞(Ω)+‖z‖W1,∞(Ω)}≤C. |
Throughout this paper we assume that
u′(t)=μuδ(1−u),u(0)=u0, |
which is ill-posed if
As preliminaries, we leave the global existence and regularity results into Section 3. Our main results concerned with the description of cell invasion processes are as follows. First, we show that the evolution of tumour invasion in the very early stage.
Theorem 2.2 (Early stage profile - upper bound). Let
suppu0⊂¯Br0(x0)⊂Ω, |
for some
suppu(⋅,t)⊂¯A(t)⊂Ω,t∈(0,t1), |
and
A(t)={x∈Ω;|x−x0|2<η(τ+t)},t∈(0,t1), |
with some appropriate
Remark 1. As a typical finite propagating model, the Barenblatt solution of the porous medium equation is
B(x,t)=(1+t)−k[(1−k(m−1)2mn|x|2(1+t)2k/n)+]1m−1 | (4) |
with
Next, we show the propagating property of the tumour cells at the early stage.
Theorem 2.3 (Early stage profile - lower bound). Let
A(t)⊂suppu(⋅,t),t>0, |
and
Remark 2. For this chemotaxis system, we proved that the tumour cells will expand to the whole body when the time
Under the hypotheses of Theorem 2.2 and Theorem 2.3, we see that there exist
A1(t)⊂suppu(⋅,t)⊂¯A2(t)⊂Ω,t∈(0,t0), |
After the tumour cells spread to the whole domain, we can investigate the large time behavior. We show that the solution converges to its steady state exponentially.
Theorem 2.4 (Late stage profile). Let
‖u(⋅,t)−1‖L∞(Ω)+‖w(⋅,t)‖W1,∞(Ω)+‖v(⋅,t)−(¯v0+¯w0)‖W2,∞(Ω)+‖z(⋅,t)−1‖L∞(Ω)≤Ce−ct, |
for all
The main difficulty lies in proving the expanding property of the support of the first component
As preliminaries, we prove the existence, boundedness and regularity of a global weak solution in this section. The main preliminary results are as follows.
Theorem 3.1 (Existence of globally bounded weak solutions). For
Theorem 3.2 (Regularity). Let
‖u‖L∞(Ω×(t,t+1))+‖v‖C2+α,1+α/2(¯Ω×[t,t+1])+‖w‖Cα(¯Ω×[t,t+1])+‖z‖W2,1p(Ω×(t,t+1))≤C(p), |
for any
We first use the artificial viscosity method to get smooth approximate solutions. Despite the absence of comparison principle, we can prove a special case compared with a lower solution, which is helpful for establishing the regularity estimates. By making use of the special structure of dispersion, we carry on the estimates on
Consider the following corresponding regularized problem
{ut=∇⋅(m(aε(u))m−1∇u)−∇⋅(um∇v)+μ|u|δ−1u(1−u)+ε,vt=Δv+wz,wt=−wz,zt=Δz−z+u,x∈Ω,t>0,∂u∂ν=∂v∂ν=∂z∂ν=0,x∈∂Ω,t>0,u(x,0)=u0ε(x),v(x,0)=v0ε(x),w(x,0)=w0ε(x),z(x,0)=z0ε(x),x∈Ω, | (5) |
where
ε≤u0ε≤u0+ε,0≤v0ε≤v0+ε,0≤w0ε≤w0+ε,0≤z0ε≤z0+ε,|∇u0ε|≤2|∇u0|,|∇v0ε|≤2|∇v0|,|∇w0ε|≤2|∇w0|,|Δw0ε|≤2|Δw0|,|∇z0ε|≤2|∇z0|, |
and
As usual, there is no comparison principle for the system, because the system is strongly coupled. However, we have the following lemma.
Lemma 3.3. There holds
Proof. We denote
Now we divide this proof into two parts. If
∇⋅(m(aε(u))m−1∇u)=m(aε(u))m−1Δu+m(m−1)a′ε(u)|∇u|2≥0,∇⋅(um∇v)=umΔv+mum−1∇u⋅∇v=0,μ|u|δ−1u(1−u−w)=0, |
which contradicts to
If
Since
∂u∂t=Δ(u+ε)m−∇⋅(um∇v)+μuδ(1−u)+ε,u≥0. |
Now we present some energy estimates independent of time
Lemma 3.4. The first solution component
supt∈(0,Tmax)∫Ωuε(⋅,t)dx≤max{∫Ωu0dx+|Ω|,(2(C1+|Ω|)μC2)1/(δ+1)}, |
where
Proof. We denote
ddt∫Ωudx≤μ∫Ωuδdx−μ∫Ωuδ+1dx+|Ω|, |
for all
μ∫Ωuδdx≤12μ∫Ωuδ+1dx+C1, |
and
∫Ωuδ+1dx≥C2(∫Ωudx)δ+1, |
where
y′(t)≤C1+|Ω|−μC22yδ+1(t). |
The comparison principle of ODE shows that
y(t)≤max{y(0),(2(C1+|Ω|)μC2)1/δ+1} |
for all
Here we recall some lemmas about the
Lemma 3.5 ([7]). Let
{q∈[1,npn−2p),p≤n2,q∈[1,∞],p>n2. |
Then for any
supt∈(0,T)‖zε(⋅,t)‖Lq(Ω)≤Cz(p,q)(‖z0‖Lq(Ω)+supt∈(0,T)‖uε(⋅,t)‖Lp(Ω)). |
Lemma 3.6 ([7]). Let
{r∈[1,nqn−q),q≤n,r∈[1,∞],q>n. |
Then for any
supt∈(0,T)‖∇vε(⋅,t)‖Lr(Ω)≤Cv(q,r)(‖∇v0‖Lr(Ω)+supt∈(0,T)‖zε(⋅,t)‖Lq(Ω)). |
Lemma 3.7. There holds
‖wε(⋅,t)‖L∞(Ω)≤‖w0‖L∞(Ω)+1,t∈(0,Tmax), |
and
∫Ωvε(x,t)dx≤∫Ωv0(x)dx+∫Ωw0(x)dx+2|Ω|,t∈(0,Tmax). |
Proof. Since both
|wε(x,t)|≤w0ε(x,t)≤‖w0‖L∞(Ω)+1. |
We add the third to the second equation of (5) and integrate over
ddt∫Ω(vε+wε)dx=∫ΩΔvεdx=0,t∈(0,Tmax). |
Thus,
∫Ω(vε+wε)dx≤∫Ωv0ε(x)dx+∫Ωw0ε(x)dx≤∫Ωv0(x)dx+∫Ωw0(x)dx+2|Ω|, |
for all
Lemma 3.8. Let
‖vε‖L∞(Ω)≤C,t∈(0,Tmax). |
For any
‖∇vε‖Lr(Ω)≤C(r),t∈(0,Tmax). |
Proof. According to Lemma 3.4,
The following Gagliardo-Nirenberg inequality (see [46,51]) will be used in deriving the
Lemma 3.9. Let
‖u‖Lp(Ω)≤C(‖∇u‖aL2(Ω)‖u‖1−aLs(Ω)+‖u‖Ls(Ω)) |
is valid with
We present the following
Lemma 3.10. Let
‖uε(⋅,t)‖Lp(Ω)≤C(p),t∈(0,Tmax). |
Proof. We denote
1r+1ddt∫Ωur+1dx+∫Ω∇(u+ε)m⋅∇urdx≤∫Ωum∇v⋅∇urdx+μ∫Ωuδ+rdx−μ∫Ωuδ+r+1dx+∫Ωurdx. | (6) |
We note that
μ∫Ωuδ+rdx≤14μ∫Ωuδ+r+1dx+C1, | (7) |
and
∫Ωurdx≤14μ∫Ωuδ+r+1dx+C2, | (8) |
where
∫Ωum∇v⋅∇urdx≤r∫Ωum+r−1|∇v⋅∇u|dx≤mr2∫Ω(u+ε)m−1ur−1|∇u|2dx+r2m∫Ωum+r|∇v|2dx≤12∫Ω∇(u+ε)m⋅∇urdx+r2m∫Ωum+r|∇v|2dx. | (9) |
We use Hölder's inequality to see that
r2m∫Ωum+r|∇v|2dx≤r2m(∫Ωum+r+κdx)m+rm+r+κ(∫Ω|∇v|2(m+r+κ)κdx)κm+r+κ≤C3(∫Ωum+r+κdx)m+rm+r+κ |
where
(∫Ωum+r+κdx)m+rm+r+κ=‖um+r2‖2L2(m+r+κ)m+r(Ω)≤C4(‖∇um+r2‖2aL2(Ω)‖um+r2‖2(1−a)L2m+r(Ω)+‖um+r2‖2L2m+r(Ω))≤C5(1+‖∇um+r2‖2aL2(Ω)), |
where
a=n(m+r)/2−n(m+r)/(2(m+r+κ))1−n/2+n(m+r)/2∈(0,1), |
provided that
r2m∫Ωum+r|∇v|2dx≤C3C5(1+‖∇um+r2‖2aL2(Ω))≤2mr(m+r)2‖∇um+r2‖2L2(Ω)+C6≤mr2∫Ω(u+ε)m−1ur−1|∇u|2dx+C6≤12∫Ω∇(u+ε)m⋅∇urdx+C6, | (10) |
since
ddt∫Ωur+1dx≤−μ(r+1)2∫Ωuδ+r+1dx+(r+1)(C1+C2+C6). |
According to
∫Ωuδ+r+1dx≥1|Ω|δr+1(∫Ωur+1dx)δ+r+1r+1, |
we obtain
ddt∫Ωur+1dx≤(r+1)(C1+C2+C6)−μ(r+1)2|Ω|δr+1(∫Ωur+1dx)δ+r+1r+1. |
By an ODE comparison,
∫Ωur+1dx≤max{∫Ω(u0+1)r+1dx,(2(C1+C2+C6)|Ω|δr+1μ)r+1δ+r+1} |
for all
Lemma 3.11. Let
supt∈(0,Tmax)‖∇vε‖L∞(Ω)≤C. |
Proof. According to Lemma 3.10,
We now employ the following Moser-type iteration to get the
Lemma 3.12. Let
supt∈(0,Tmax)‖uε‖L∞(Ω)≤C. |
Proof. We denote
1r+1ddt∫Ωur+1dx+∫Ω∇(u+ε)m⋅∇urdx≤∫Ωum∇v⋅∇urdx+μ∫Ωuδ+rdx−μ∫Ωuδ+r+1dx+∫Ωurdx. | (11) |
Similar to the proof of Lemma 3.10, using Young's inequality we can estimate
μ∫Ωuδ+rdx≤14μ∫Ωuδ+r+1dx+4δ+rμ|Ω|,∫Ωurdx≤14μ∫Ωuδ+r+1dx+(4μ)rδ+r|Ω|, |
and
∫Ωum∇v⋅∇urdx≤r∫Ωum+r−1|∇v⋅∇u|dx≤mr4∫Ω(u+ε)m−1ur−1|∇u|2dx+rm∫Ωum+r|∇v|2dx≤14∫Ω∇(u+ε)m⋅∇urdx+rm‖∇v‖2L∞(Ω)∫Ωum+rdx, | (12) |
where according to Lemma 3.11
∫Ωum+rdx=‖um+r2‖2L2(Ω)≤C0(‖∇um+r2‖2aL2(Ω)‖um+r2‖2(1−a)L1(Ω)+‖um+r2‖2L1(Ω)), |
where
rm‖∇v‖2L∞(Ω)∫Ωum+rdx≤rm‖∇v‖2L∞(Ω)C0(‖∇um+r2‖2aL2(Ω)‖um+r2‖2(1−a)L1(Ω)+‖um+r2‖2L1(Ω))≤mr(m+r)2‖∇um+r2‖2L2(Ω)+(rm‖∇v‖2L∞(Ω)C0)11−a((m+r)2mr)a1−a‖um+r2‖2L1(Ω)+rm‖∇v‖2L∞(Ω)C0‖um+r2‖2L1(Ω)≤14∫Ω∇(u+ε)m⋅∇urdx+C1(r)‖um+r2‖2L1(Ω), | (13) |
where
C1(r)=(rm‖∇v‖2L∞(Ω)C0)11−a((m+r)2mr)a1−a+rm‖∇v‖2L∞(Ω)C0. |
Inserting the above estimates (12), (13) into (11) yields
ddt∫Ωur+1dx+∫Ωur+1dx≤C1(r)(r+1)‖um+r2‖2L1(Ω)+(r+1)(4δ+rμ|Ω|+(4μ)rδ+r|Ω|)+∫Ωur+1dx−12μ∫Ωuδ+r+1dx≤C1(r)(r+1)‖um+r2‖2L1(Ω)+C2(r), | (14) |
where
C2(r)=(r+1)(4δ+rμ|Ω|+(4μ)rδ+r|Ω|)+(2μ)r+1δ|Ω|. |
Now we use the following Moser-type iteration. Let
rj−1+1=rj+m2,j∈N+. |
We can invoke Lemma 3.10 to find
supt∈(0,Tmax)‖u‖Lr1+1(Ω)≤C0. |
From (14) and an ODE comparison, we have
supt∈(0,Tmax)‖u‖rj+1Lrj+1(Ω)≤max{∫Ω(u0+1)rj+1dx,C1(rj)(rj+1)⋅supt∈(0,Tmax)‖u‖2(rj−1+1)Lrj−1+1(Ω)+C2(rj)}. | (15) |
A simple analysis shows that
supt∈(0,Tmax)‖u‖rj+1Lrj+1(Ω)≤max{∫Ω(u0+1)rj+1dx,a1rb1j⋅supt∈(0,Tmax)‖u‖2(rj−1+1)Lrj−1+1(Ω)+a2brj2}. | (16) |
Let
Mj=max{supt∈(0,Tmax)∫Ωurj+1dx,1}. |
Since boundedness of
Mj≤a1rb1jM2j−1+a2brj2. | (17) |
We note that if
M1rj−1+1j−1≤(a2brj2)12(rj−1+1)≤a1rj+m2brjrj+m2≤2b2, |
for
M2j−1≥a2brj2,j≥j0. |
Therefore, we can rewrite (17) into
Mj≤2a1rb1jM2j−1≤DjM2j−1 | (18) |
for all
Mj≤D∑j−2i=0(j−i)⋅2j⋅M2j−11=D2j+2j−1−j−2M2j−11≤D2j+1M2j−11 |
for all
M1rj+1j≤D2j+12j+m−1M2j−12j+m−10≤D2M1, |
for all
Now we turn to the regularity estimates.
Lemma 3.13. Let
supt∈(0,Tmax)(‖zε‖L∞(Ω)+‖∇zε‖L∞(Ω)+‖vε‖L∞(Ω)+‖∇vε‖L∞(Ω))≤C. |
And the third solution component
‖∇wε(⋅,t)‖L∞(Ω)≤2‖∇w0‖L∞(Ω)+(‖w0‖L∞(Ω)+1)supt∈(0,Tmax)‖∇zε‖L∞(Ω)t, |
for all
Proof. According to Lemma 3.12, Lemma 3.5, Lemma 3.6, we see that
w(x,t)=w0ε(x)e−∫t0z(x,τ)dτ,∇w(x,t)=∇w0ε(x)e−∫t0z(x,τ)dτ−w0ε(x)e−∫t0z(x,τ)dτ∫t0∇z(x,τ)dτ. |
Therefore,
|∇w(x,t)|≤|∇w0ε(x,t)|+w0ε(x)supt∈(0,Tmax)‖∇z‖L∞(Ω)t≤2‖∇w0‖L∞(Ω)+(‖w0‖L∞(Ω)+1)supt∈(0,Tmax)‖∇zε‖L∞(Ω)t. |
This completes the proof.
Lemma 3.14. There exists a constant
∫T0∫Ω|Δvε|2dxdt≤C(1+T2),T∈(0,Tmax). |
Proof. We denote
∫Ω∂∂t|∇v|2dx+∫Ω|Δv|2dx=∫Ω∇v⋅∇(wz)dx≤C(∫Ω|∇w|dx+1)≤C(1+t), |
since
Lemma 3.15. There exists a constant
∫T0∫Ω|∇umε|2dxdt≤C(1+T),T∈(0,Tmax). |
Proof. We denote
1m+1ddt∫Ω(u+ε)m+1dx+∫Ω|∇(u+ε)m|2dx≤∫Ωum∇v⋅∇(u+ε)mdx+μ∫Ωuδ(u+ε)mdx−μ∫Ωuδ+1(u+ε)mdx+∫Ω(u+ε)mdx. | (19) |
According to Lemma 3.11 and Lemma 3.12,
∫Ωum∇v⋅∇(u+ε)mdx≤12∫Ω|∇(u+ε)m|2dx+C1, |
where
∫Ω(u+ε)m+1dx+∫T0∫Ω|∇(u+ε)m|2dx≤∫Ω(u0ε+ε)m+1dx+CT. | (20) |
We note that
|∇um|=mum−1|∇u|≤m(u+ε)m−1|∇(u+ε)|=|∇(u+ε)m|. |
This completes the proof.
Lemma 3.16. There exists a constant
∫T0∫Ω|(um+12ε)t|2dxdt+∫Ω|∇umε|2dx≤C(1+T2),T∈(0,Tmax). |
Moreover,
∫T0∫Ω|(umε)t|2dxdt≤4m2(m+1)2‖uε‖m−1L∞(Ω)∫T0∫Ω|(um+12ε)t|2dxdt≤C(1+T2), |
for all
Proof. We denote
∫Ωm(u+ε)m−1|ut|2dx+∫Ω∇(u+ε)m⋅∇[(u+ε)m]tdx≤∫Ωum∇v⋅∇[(u+ε)m]tdx+μ∫Ωuδ[(u+ε)m]tdx−μ∫Ωuδ+1[(u+ε)m]tds+∫Ω|[(u+ε)m]t|dx. | (21) |
We note that
∫Ωμuδ[(u+ε)m]tdx=∫Ωmμuδ(u+ε)m−1utdx≤15∫Ωm(u+ε)m−1|ut|2dx+C1,∫Ω−μuδ+1[(u+ε)m]tdx=−∫Ωmμuδ+1(u+ε)m−1utdx≤15∫Ωm(u+ε)m−1|ut|2dx+C2,∫Ω|[(u+ε)m]t|dx=∫Ωm(u+ε)m−1utdx≤15∫Ωm(u+ε)m−1|ut|2dx+C3, |
where
∫Ωm(u+ε)m−1|ut|2dx=4m(m+1)2∫Ω|((u+ε)m+12)t|2dx, |
and
∫Ω∇(u+ε)m⋅∇[(u+ε)m]tdx=12∂∂t∫Ω|∇(u+ε)m|2dx. |
There holds
∫Ωum∇v⋅∇[(u+ε)m]tdx=−∫Ω[(u+ε)m]t∇⋅(um∇v)dx=−∫Ωm(u+ε)m−1ut⋅(mum−1∇u⋅∇v+umΔv)dx≤15∫Ωm(u+ε)m−1|ut|2dx+C4∫Ω(u+ε)2(m−1)|∇u|2dx+C5∫Ω|Δv|2dx≤15∫Ωm(u+ε)m−1|ut|2dx+C4∫Ω|∇(u+ε)m|2dx+C5∫Ω|Δv|2dx, |
where
∫T0∫Ω|((u+ε)m+12)t|2dxdt+∫Ω|∇(u+ε)m|2dx≤∫Ω|∇(u0ε+ε)m|2dx+C(1+T2)≤C(1+T2). |
Clearly, we have
|(um+12)t|2=(m+1)24um−1|ut|2≤(m+1)24(u+ε)m−1|ut|2=|((u+ε)m+12)t|2, |
and
|(um)t|2≤4m2(m+1)2‖uε‖m−1L∞(Ω)|(um+12)t|2≤4m2(m+1)2‖uε‖m−1L∞(Ω)|((u+ε)m+12)t|2. |
The proof is completed.
Proof of Theorem 3.1. According to the estimates, for any
Now we show the regularity of the globally bounded weak solution.
Lemma 3.17. Let
supt∈R+{‖u‖L∞(Ω)+‖v‖W1,∞(Ω)+‖w‖L∞(Ω)+‖z‖W1,∞(Ω)}≤C. |
Proof. Since
In Lemma 3.13, we have proved
Lemma 3.18. Let
∫Ω|∇w(⋅,t)|pdx≤C(p),t>0, |
for some constant
Proof. This proof proceeds along the idea of the arguments of Lemma 4.3 in [47] and Lemma 4.1 in [40]. Since
w(x,t)=w0(x)e−∫t0z(x,s)ds, |
and
∇w(x,t)=∇w0(x)e−∫t0z(x,s)ds−w0(x)e−∫t0z(x,s)ds∫t0∇z(x,s)ds. |
We see that
|∇w(x,t)|2≤2|∇w0(x)|2e−2∫t0z(x,s)ds+2|w0(x)|2e−2∫t0z(x,s)ds|∫t0∇z(x,s)ds|2. |
And thus
∫Ω|∇w(x,t)|2dx≤C+C∫Ωe−2∫t0z(x,s)ds|∫t0∇z(x,s)ds|2dx≤C−C2∫Ω∇e−2∫t0z(x,s)ds⋅(∫t0∇z(x,s)ds)dx≤C+C2∫Ωe−2∫t0z(x,s)ds⋅(∫t0Δz(x,s)ds)dx≤C+C2∫Ωe−2∫t0z(x,s)ds⋅(∫t0(zt+z−u)ds)dx≤C+C2∫Ωe−2∫t0z(x,s)ds⋅(z(x,t)+∫t0z(x,s)ds)dx≤C. |
Using the same method, we have
|∇w(x,t)|4≤23|∇w0(x)|4e−4∫t0z(x,s)ds+23|w0(x)|4e−4∫t0z(x,s)ds|∫t0∇z(x,s)ds|4, |
and
∫Ω|∇w(x,t)|4dx≤C+C∫Ωe−4∫t0z(x,s)ds|∫t0∇z(x,s)ds|4dx≤C−C4∫Ω∇e−4∫t0z(x,s)ds⋅(∫t0∇z(x,s)ds)3dx≤C+3C4∫Ωe−4∫t0z(x,s)ds⋅(∫t0∇z(x,s)ds)2⋅(∫t0Δz(x,s)ds)dx≤C+3C4∫Ωe−4∫t0z(x,s)ds⋅(∫t0∇z(x,s)ds)2⋅(∫t0(zt+z−u)ds)dx≤C+3C4∫Ωe−4∫t0z(x,s)ds⋅(∫t0∇z(x,s)ds)2⋅(z(x,t)+∫t0z(x,s)ds)dx≤C+3C4∫Ωe−2∫t0z(x,s)ds⋅(∫t0∇z(x,s)ds)2dx⋅supx∈Ω[e−2∫t0z(x,s)ds⋅(z(x,t)+∫t0z(x,s)ds)]≤C, |
according to the proof of the previous estimate on
Proof of Theorem 3.2. Lemma 3.18 shows the uniform bound of
‖w‖Cα(¯Ω×[t,t+1])≤C,t>0. |
Since
‖zt‖Lp(Ω×(t,t+1))+‖Δz‖Lp(Ω×(t,t+1))≤C(p),t>0, |
for some constant
‖z‖Cα(¯Ω×[t,t+1])≤C,t>0. |
Thus,
‖wz‖Cα(¯Ω×[t,t+1])≤C,t>0. |
This can also be deduced by
‖∇(wz)‖Lp(Ω)+‖(wz)t‖Lp(Ω×(t,t+1))≤C,t>0, |
with
‖v‖C2+α,1+α/2(¯Ω×[t,t+1])+‖z‖W2,1p(Ω×(t,t+1))≤C(p). |
The proof is completed.
This section is devoted to the study of the propagating properties of the tumour cells and the large time behavior of the weak solution
We first present the following comparison principle of the first component.
Lemma 4.1. Let
E={u∈L∞(QT);u≥0,∇um∈L2((0,T);L2(Ω)),um−1ut∈L2((0,T);L2(Ω))}, |
{∂u1∂t≥Δum1−∇⋅(um1∇v)+μuδ1(1−u1),∂u2∂t≤Δum2−∇⋅(um2∇v)+μuδ2(1−u2),x∈Ω,t∈(0,T),∂u1∂ν≥0≥∂u2∂ν,x∈∂Ω,t∈(0,T),u1(x,0)≥u2(x,0)≥0,x∈Ω, |
in the sense that the following inequalities
∫T0∫Ωu1φtdxdt+∫Ωu10(x)φ(x,0)dx≤∫T0∫Ω∇um1⋅∇φdxdt−∫T0∫Ωum1∇v⋅∇φdxdt−∫T0∫Ωμuδ1(1−u1)φdxdt,∫T0∫Ωu2φtdxdt+∫Ωu20(x)φ(x,0)dx≥∫T0∫Ω∇um2⋅∇φdxdt−∫T0∫Ωum2∇v⋅∇φdxdt−∫T0∫Ωμuδ2(1−u2)φdxdt, |
hold for some fixed
Proof. The following inequality
∫T0∫Ω(u1−u2)φtdxdt≤∫T0∫Ω∇(um1−um2)⋅∇φdxdt−∫T0∫Ω(um1−um2)∇v⋅∇φdxdt−∫T0∫Ωμ(uδ1(1−u1)−uδ2(1−u2))φdxdt, |
holds for all
a(x,t)={um1−um2u1−u2,u1(x,t)≠u2(x,t),mum−11,u1(x,t)=u2(x,t), |
b(x,t)={(um1−um2)∇vu1−u2,u1(x,t)≠u2(x,t),mum−11∇v,u1(x,t)=u2(x,t), |
and
c(x,t)={μ(uδ1(1−u1)−uδ2(1−u2))u1−u2,u1(x,t)≠u2(x,t),μδuδ−11−μ(δ+1)uδ1,u1(x,t)=u2(x,t). |
Since
∫T0∫Ω(u1−u2)(φt+a(x,t)Δφ+b(x,t)⋅∇φ+c(x,t)φ)dxdt≤0. |
We employ the standard duality proof method or the approximate Hohmgren's approach to complete this proof (see Theorem 6.5 in [43], Chapter 1.3 and 3.2 in [56]). For any smooth function
{φt+(κ+aε(x,t))Δφ+b(x,t)⋅∇φ+cθ(x,t)φ+ψ=0,(x,t)∈QT,∂φ∂ν=0,(x,t)∈∂Ω×(0,T),φ(x,T)=0,x∈Ω, | (22) |
where
cθ(x,t)={μ(uδ1(1−u1)−uδ2(1−u2))u1−u2,|u1(x,t)−u2(x,t)|≥θ,0,|u1(x,t)−u2(x,t)|<θ. |
This definition of
c2θa≤C(θ). |
We may also need to replace
∬QT(u1−u2)ψdxdt≥−∬QT|u1−u2||a−aε||Δφ|dxdt−κ∬QT|u1−u2||Δφ|dxdt−∬QT|u1−u2||c−cθ|φdxdt=:−I1−I2−I3. |
Now we need the a priori estimate on
∬QTφtηΔφdxdt+∬QTη(κ+aε)(Δφ)2dxdt≤∬QTη|b||∇φ||Δφ|dxdt+∬QTηcθφΔφdxdt+∬QTηψΔφdxdt≤∬QTηCa|∇φ||Δφ|dxdt+14∬QTη(κ+aε)(Δφ)2dxdt+∬QTηc2θφ2κ+aεdxdt+∬QTη|∇ψ||∇φ|dxdt≤12∬QTη(κ+aε)(Δφ)2dxdt+∬QTηC2a2|∇φ|2κ+aεdxdt+∬QTηC(θ)φ2dxdt+∬QTη|∇ψ|2dxdt+∬QTη|∇φ|2dxdt. |
Using
∬QTφtηΔφdxdt=−∬QTη∇φ⋅∇φtdxdt=−12∬QTη∂∂t|∇φ|2dxdt≥12∬QTη′(t)|∇φ|2dxdt≥M2∬QT|∇φ|2dxdt. |
Therefore,
∬QT|∇φ|2dxdt+∬QT(κ+aε)(Δφ)2dxdt≤C(θ). | (23) |
It follows that
I1=∬QT|u1−u2||a−aε||Δφ|dxdt≤(∬QT(κ+aε)|Δφ|2dxdt)12⋅(∬QT|a−aε|2κ+aε|u1−u2|2dxdt)12≤C(θ)(∬QT|a−aε|2κ+aεdxdt)12≤C(θ)κ12(∬QT|a−aε|2dxdt)12, |
which converges to zero if we let
Fγ={(x,t)∈QT;|u1−u2|≥γ}, |
and
Gγ={(x,t)∈QT;|u1−u2|<γ}. |
Then there exists a constant
I2=κ∬QT|u1−u2||Δφ|dxdt≤κ∬Gγ|u1−u2||Δφ|dxdt+κ∬Fγ|u1−u2||Δφ|dxdt≤γ∬Gγκ|Δφ|dxdt+CκC(γ)12∬Fγa12|Δφ|dxdt≤Cγ(∬QTκ|Δφ|2dxdt)12+CκC(γ)12(∬QTa|Δφ|2dxdt)12≤γC(θ)+κC(θ)C(γ)12, |
which converges to zero if we first let
I3=∬QT|u1−u2||c−cθ|φdxdt≤C(∬QT|c−cθ|2dxdt)12, |
which converges to zero if we let
∬QT(u1−u2)ψdxdt≥0 |
for any given
Here we recall some lemmas about the asymptotic behavior of solutions to evolutionary equations.
Lemma 4.2 ([7]). Let
‖v(⋅,t)−L‖W1,∞(Ω)→0,ast→∞. |
In particular,
‖∇v(⋅,t)‖L∞(Ω)→0,ast→∞. |
Lemma 4.3 ([47] Lemma 4.1). If
{zt=Δz−z+u,x∈Ω,t>0,∂z∂ν=0,x∈∂Ω,t>0,z(x,0)=z0(x),x∈Ω, |
where
∫t0z(x,s)ds≥C1∫t0∫Ωu(y,s)dyds−C2,x∈Ω,t>0. |
Lemma 4.4 ([47] Lemma 4.3, [40] Lemma 4.1). If
{wt=−wz,zt=Δz−z+u,x∈Ω,t>0,∂z∂ν=0,x∈∂Ω,t>0,w(x,0)=w0(x),z(x,0)=z0(x),x∈Ω, |
with
∫Ω|∇w(⋅,t)|2dx≤2∫Ω|∇w0|2dx+|Ω|2e‖w0‖2L∞(Ω)+‖w0‖2L∞(Ω)∫Ωz(⋅,t)dx |
for all
Now we construct a self similar weak lower solution with expanding support.
Lemma 4.5. Let
g(x,t)=ε(1+t)−κ[(η−|x−x0|2(1+t)β)+]d,x∈Ω,t≥0, |
where
{∂g∂t≤Δgm−∇⋅(gm∇v)+μgδ(1−g),x∈Ω,t∈(0,T),∂g∂ν≤0,x∈∂Ω,t∈(0,T),0≤g(x,0)≤u0(x),x∈Ω, |
in the sense that the following inequality
∫T0∫Ωgφtdxdt+∫Ωg(x,0)φ(x,0)dx≥∫T0∫Ω∇gm⋅∇φdxdt−∫T0∫Ωgm∇v⋅∇φdxdt−∫T0∫Ωμgδ(1−g)φdxdt, |
holds for any
Proof. For simplicity, we let
h(x,t)=(η−|x−x0|2(1+t)β)+,x∈Ω,t≥0, |
and
A(t)={x∈Ω;|x−x0|2(1+t)β<η},t≥0. |
Since
gt=−κε(1+t)−κ−1hd+ε(1+t)−κdhd−1β|x|2(1+t)β+1,∇gm=−εm(1+t)−mκmdhmd−12x(1+t)β,Δgm=εm(1+t)−mκmd(md−1)hmd−24|x|2(1+t)2β−εm(1+t)−mκmdhmd−12n(1+t)β, |
for all
g(x,0)=ε[(η−|x|2)+]d≤ε11Br(x0)≤u0(x),x∈Ω, |
provided that
η≤r2,εηd≤ε1. | (24) |
In order to find a weak lower solution
∂g∂t≤Δgm−∇⋅(gm∇v)+μgδ(1−g),x∈A(t),t>0. | (25) |
Since
|∇⋅(gm∇v)|≤gm|Δv|+|mgm−1||∇g||∇v|≤gm‖Δv‖L∞(Ω×R+)+(m+1)|∇gm|⋅‖∇v‖L∞(Ω×R+). |
We denote
ε(1+t)−κdhd−1β|x|2(1+t)β+1+εm(1+t)−mκmdhmd−12n(1+t)β+C2εm(1+t)−mκhmd+(m+1)C1εm(1+t)−mκmdhmd−12|x|(1+t)β≤κε(1+t)−κ−1hd+εm(1+t)−mκmd(md−1)hmd−24|x|2(1+t)2β+μ2εδ(1+t)−κδhdδ,x∈A(t),t>0. | (26) |
As we have chosen
εβm−1|x|2(1+t)β+2nmm−1εmh+C2εm(1+t)βh2+2(m+1)C1εmmm−1h|x|≤κεh+εmm(m−1)24|x|2(1+t)β+μ2εδ(1+t)−κδ+κ+1hdδ−d+1,x∈A(t),t>0. | (27) |
Let
{εβ≤4εmmm−1,2nmm−1εm≤12κε,2mC1εm|x|≤12κε,C2εmhd+1−dδ≤μ2εδ(1+t)−κδ+κ+1−β,x∈A(t),t>0. | (28) |
Since
ε=min{(18nm)1m−1,(18m(m−1)C1diamΩ)1m−1,ε1r2d,(μ2C2)1m−δ}, |
and then
Now, we find a weak lower solution with expanding support and comparison principle Lemma 4.1 implies
u(x,t)≥g(x,t)=ε(1+t)−κ[(η−|x−x0|2(1+t)β)+]d,x∈Ω,t>0. |
There exists a
η−|x−x0|2(1+t0)β≥η2,x∈Ω, |
and thus
u(x,t0)≥g(x,t0)≥ε(1+t0)−κ(η2)d,x∈Ω. |
Next, we construct another constant lower solution
u_(x,t)≡ε0,x∈Ω,t>t0, |
with
0≤−εm0Δv(x,t)+μεδ0(1−ε0),x∈Ω,t>t0, |
which is valid if we further let
ε0≤(μ2‖Δv‖L∞(Ω×(t0,+∞)))1m−δ, |
since
u(x,t)≥u_(x,t)≡ε0,x∈Ω,t>t0. |
This completes the proof.
Remark 3. It is interesting to compare the self similar weak lower solution
B(x,t)=(1+t)−k[(1−k(m−1)2mn|x|2(1+t)2k/n)+]1m−1, |
with
Proof of Theorem 2.3. This has been proved in Lemma 4.5.
After proving the support expanding property of the first equation in (3), which is a degenerate diffusion equation, we can deduce the following convergence properties of all components.
Lemma 4.6. Let
‖w(⋅,t)‖L∞(Ω)+‖∇w(⋅,t)‖L∞(Ω)≤C1e−c1t, |
and
‖v(⋅,t)−(¯v0+¯w0)‖L∞(Ω)+‖∇v(⋅,t)‖L∞(Ω)+‖Δv(⋅,t)‖L∞(Ω)≤C2e−c2t, |
for all
Proof. Applying Lemma 4.3, we see that
∫t0z(x,t)ds≥C∫t0∫Ωu(y,s)dyds−C≥C∫tt0∫Ωu(y,s)dyds−C≥C|Ω|ε0(t−t0)−C≥c1t−C,x∈Ω,t>t0, |
since
w(x,t)=w0(x)e−∫t0z(x,s)ds≤w0(x)e−c1t+C≤C1e−c1t,x∈Ω,t>t0. | (29) |
This is also valid for
|∇w(x,t)|=|∇w0(x)|e−∫t0z(x,s)ds+w0(x)e−∫t0z(x,s)ds|∫t0∇z(x,s)ds|≤Ce−c1t+Ce−c1tt≤C′1e−c′1t,x∈Ω,t>t0, |
with
|∇(wz)(x,t)|≤|z∇w(x,t)|+|w∇z(x,t)|≤Ce−c1t,x∈Ω,t>t0, |
It follows form the second equation in (3) that
v(x,t)=etΔv0+∫t0e(t−s)Δ(wz)(⋅,s)ds,t>0, |
and
∇v(x,t)=etΔ∇v0+∫t0e(t−s)Δ∇(wz)(⋅,s)ds,t>0, |
Using the standard
‖Δv(x,t)‖L∞(Ω)≤‖∇etΔ|∇v0|‖L∞(Ω)+∫t0‖∇e(t−s)Δ|∇(wz)(x,s)|‖L∞(Ω)ds≤C(1+t−12)e−λ1t‖∇v0‖L∞(Ω)+C∫t0(1+(t−s)−12)e−λ1(t−s)‖∇(wz)(⋅,s)‖L∞(Ω)≤Ce−λ1t+C∫t0(1+(t−s)−12)e−λ1(t−s)e−c1sds≤C2e−c2t,x∈Ω,t>t0, |
where
∫Ω(v(x,t)+w(x,t))dx≡∫Ω(v0(x)+w0(x))dx, |
which is the same as the estimate of
¯v(t)=1|Ω|∫Ωv(x,t)dx |
is converging to
‖v(x,t)−¯v(t)‖L∞(Ω)≤C‖∇v(x,t)‖L∞(Ω)≤Ce−c2t. |
Therefore,
‖v(x,t)−(¯v0+¯w0)‖L∞(Ω)≤‖v(x,t)−¯v(t)‖L∞(Ω)+‖¯v(t)−(¯v0+¯w0)‖L∞(Ω)≤‖v(x,t)−¯v(t)‖L∞(Ω)+‖¯w(t)‖L∞(Ω)≤Ce−c′2t,x∈Ω,t>t0, |
The proof is completed.
Lemma 4.7. For constants
{g′(t)=Ce−ctgm,t>0,g(0)=g0>0, |
blows up in finite time if
Proof. There holds
−1m−1(1gm−1)′=Ce−ct,t>0. |
Integrating over
1m−1(1gm−10−1gm−1(t))=Cc(1−e−ct). |
A simple analysis completes this proof.
Lemma 4.8. Let
‖u(⋅,t)−1‖L∞(Ω)≤C3e−c3t, |
for all
Proof. Lemma 4.5 implies that
{u′1(t)≥um1‖Δv(⋅,t)‖L∞(Ω)+μuδ1(1−u1),u′2(t)≤−um2‖Δv(⋅,t)‖L∞(Ω)+μuδ2(1−u2),t>t1,u1(t1)≥‖u(⋅,t1)‖L∞(Ω),u2(t1)≤ε0. | (30) |
Lemma 4.1 shows that
u1(t)≥u(x,t)≥u2(t),x∈Ω,t>t0. |
We only need to find one pair of
{u′1(t)=C2e−c2tum1+μuδ1(1−u1),u′2(t)=−C2e−c2tum2+μuδ2(1−u2),t>t1,u1(t1)=‖u(⋅,t1)‖L∞(Ω)+1,u2(t1)=ε0, | (31) |
since
c2C2e−c2t1>2(m−1)(supt>0‖u(⋅,t)‖L∞(Ω)+1)m−1. |
Lemma 4.7 implies that
{u′1(t)≤CmC2e−c2t+μεδ0(1−u1),t>t1,u1(t1)=‖u(⋅,t1)‖L∞(Ω)+1. |
We see that
{¯u′1(t)=CmC2e−c2t+μεδ0(1−¯u1),t>t1,¯u1(t1)=‖u(⋅,t1)‖L∞(Ω)+1, | (32) |
which can be solved as
¯u1(t)=1+e−μεδ0(t−t1)(‖u(⋅,t1)‖L∞(Ω)+1)+CmC2∫tt1e−μεδ0(t−s)e−c2sds−e−μεδ0(t−t1)≤1+e−μεδ0(t−t1)‖u(⋅,t1)‖L∞(Ω)+CmC2Ce−min{μεδ0,c2}t/2,t>t1. |
On the other hand, the lower solution of
{u′2(t)=−C2e−c2tum2+μuδ2(1−u2),t>t1,u2(t1)=ε0. |
We note that we can choose
C2e−c2tεm0≤μεδ0(1−ε0). |
An ODE comparison shows that
{u′2(t)≥−C2e−c2t+μεδ0(1−u2),t>t1,u2(t1)=ε0. |
We see that
{u_′2(t)=−C2e−c2t+μεδ0(1−u_2),t>t1,u_2(t1)=ε0. |
This can also be solved as
u_2(t)=1+e−μεδ0(t−t1)ε0−C2∫tt1e−μεδ0(t−s)e−c2sds−e−μεδ0(t−t1)≥1−e−μεδ0(t−t1)−C2Ce−min{μεδ1,c2}t/2,t>t1. |
Thus, we conclude
u_2(t)≤ut(t)≤u(x,t)≤ut(t)≤¯u1(t),t>t1, |
and
Lemma 4.9. Let
‖z(⋅,t)−1‖L∞(Ω)≤C4e−c4t, |
for all
Proof. From the fourth equation in (3), we have
z(x,t)=et(Δ−1)z0+∫t0e(t−s)(Δ−1))u(⋅,s)ds,t>0. |
We note that
∫t0e(t−s)(Δ−1))1ds=1−e−t, |
which can be deduced by solving the ODE
‖z(x,t)−1‖L∞(Ω)≤‖et(Δ−1)z0‖L∞(Ω)+∫t0‖e(t−s)(Δ−1))(u(⋅,s)−1)‖L∞(Ω)ds+e−t≤Ce−t(‖z0‖L∞(Ω)+1)+C∫t0e−(t−s)‖(u(⋅,s)−1)‖L∞(Ω)ds≤Ce−t+CC3∫t0e−(t−s)e−c3sds≤C4e−c4t,t>0. |
The proof is completed.
Proof of Theorem 2.4. This is proved by collecting Lemma 4.5, Lemma 4.6, Lemma 4.8 and Lemma 4.9.
Finally, we construct a self similar upper solution with expanding support to prove Theorem 2.2. We note that for constructing a weak upper solution for the heat equation, one should replace the cut-off composite function
Lemma 4.10. Let
suppu0⊂¯Br0(x0)⊂Ω, |
for some
g(x,t)=ε(τ+t)σ[(η−|x−x0|2(τ+t)β)+]d,x∈Ω,t≥0, |
where
{∂g∂t≥Δgm−∇⋅(gm∇v)+μgδ(1−g),x∈Ω,t∈(0,t0),∂g∂ν≥0,x∈∂Ω,t∈(0,t0),g(x,0)≥u0(x)≥0,x∈Ω, |
in the sense that the following inequality
∫t00∫Ωgφtdxdt+∫Ωg(x,0)φ(x,0)dx≤∫t00∫Ω∇gm⋅∇φdxdt−∫t00∫Ωgm∇v⋅∇φdxdt−∫t00∫Ωμgδ(1−g)φdxdt, |
holds for all test functions
suppu(⋅,t)⊂¯A(t)⊂Ω,t∈(0,t0), |
and
Proof. For simplicity, we let
h(x,t)=(η−|x−x0|2(τ+t)β)+,x∈Ω,t≥0, |
and
A(t)={x∈Ω;|x−x0|2(τ+t)β<η},t≥0. |
Since
gt=σε(τ+t)σ−1hd+ε(τ+t)σdhd−1β|x|2(τ+t)β+1,∇gm=−εm(τ+t)mσmdhmd−12x(τ+t)β,Δgm=εm(τ+t)mσmd(md−1)hmd−24|x|2(τ+t)2β−εm(τ+t)mσmdhmd−12n(τ+t)β, |
for all
r2=r0+r12,η=r22τβ,t0=min{τ,τ((r1r2)2β−1)}. | (33) |
According to the definition of
g(x,0)=ετσ[(η−|x−x0|2τβ)+]d≥ετσ(r22τβ−r20τβ)d⋅1Br0(x0)≥ε11Br0(x0)≥u0(x),x∈Ω, |
provided that
ετσ(r22τβ−r20τβ)d≥ε1. | (34) |
In order to find a weak lower solution
∂g∂t≥Δgm−∇⋅(gm∇v)+μgδ(1−g),x∈A(t),t∈(0,t0). | (35) |
Since
|∇⋅(gm∇v)|≤gm|Δv|+|mgm−1||∇g||∇v|≤gm‖Δv‖L∞(Ω×R+)+(m+ετσηd)|∇gm|⋅‖∇v‖L∞(Ω×R+). |
We denote
σε(τ+t)σ−1hd+ε(τ+t)σdhd−1β|x|2(τ+t)β+1+εm(τ+t)mσmdhmd−12n(τ+t)β≥C2εm(τ+t)mσhmd+(m+ετσηd)C1εm(τ+t)mσmdhmd−12|x|(τ+t)β+εm(τ+t)mσmd(md−1)hmd−24|x|2(τ+t)2β+μεδ(τ+t)δσhdδ, | (36) |
for all
σε(τ+t)σ−1h+εβm−1(τ+t)σ|x|2(τ+t)β+1+2nmm−1εm(τ+t)mσh(τ+t)β≥C2εm(τ+t)mσh2+2(m+ετσηd)C1εm(τ+t)mσmdh|x|(τ+t)β+m(m−1)2εm(τ+t)mσ4|x|2(τ+t)2β+μεδ(τ+t)δσhdδ−d+1,x∈A(t),t∈(0,t0). |
Let
{12εβm−1(τ+t)σ|x|2(τ+t)β+1≥m(m−1)2εm(τ+t)mσ4|x|2(τ+t)2β,13σε(τ+t)σ−1h≥C2εm(τ+t)mσh2,13σε(τ+t)σ−1h≥μεδ(τ+t)δσhdδ−d+1,12εβm−1(τ+t)σ|x|2(τ+t)β+1+13σε(τ+t)σ−1h≥2(m+ετσηd)C1εm(τ+t)mσmdh|x|(τ+t)β,x∈A(t),t∈(0,t0). | (37) |
We have the following estimate
2(m+ετσηd)C1εm(τ+t)mσmdh|x|(τ+t)β≤m(m−1)2εm(τ+t)mσ4|x|2(τ+t)2β+(m+ετσηd)2C21mεm(τ+t)mσh2, |
for all
{(m−1)β≥8mεm−1(τ+t)(m−1)σ−β+1,2σ/3≥(C2+(m+ετσηd)2C21m)εm−1(τ+t)(m−1)σ+1h,σ/3≥μεδ−1(τ+t)(δ−1)σ+1hd(δ−1),x∈A(t),t∈(0,t0). | (38) |
We note that
ε=ε1τσ−dβ(r22−r20)d:=C3τdβ−σ. |
Now, we only need to find
{(m−1)β≥8mCm−132max{0,(m−1)σ−β+1}τ,2σ/3≥(C2+(m+C3r2d2)2C21m)Cm−132(m−1)σ+1r22τ,σ/3≥μCδ−132(δ−1)σ+1r2d(δ−1)2τ. |
This can be done by selecting
The comparison principle Lemma 4.1 implies that
suppu(⋅,t)⊂¯A(t)={x∈Ω;|x−x0|2<η(τ+t)β},t∈(0,t0), |
and
∂A(t)={x∈Ω;|x−x0|=η12(τ+t)β2},t∈(0,t0), |
which has finite derivative with respect to
Remark 4. Similar to the weak lower solution in Lemma 4.5, we compare the self similar weak upper solution
B(x,t)=(1+t)−k[(1−k(m−1)2mn|x|2(1+t)2k/n)+]1m−1, |
with
Remark 5. From the proof of Lemma 4.10, we can choose
Proof of Theorem 2.2. This has been proved in Lemma 4.10.
In this section, we extend the derivation of the classical taxis models in [36]. The derivation of the model begins with a master equation for a continuous-time and discrete-space random walk
∂ui∂t=T+i−1ui−1+T−i+1ui+1−(T+i+T−i)ui, | (39) |
where
Painter and Hillen [11,28] proposed volume filling approach. In this model, the transitional probability then takes the form
T±i=q(ui±1)(α+β(τ(vi±1)−τ(vi))), | (40) |
where
∂u∂t=∇⋅(d1(q(u)−q′(u))∇u−χ(v)q(u)u∇u) |
where
Since a different combination of the above strategies may be necessary to reflect cell movement, we combine the local and gradient-based strategies and assume the transitional probability of the form
T±i=q(ui)(α+β(τ(vi±1)−τ(vi))), | (41) |
where
q(0)=0,q(1)=1andq(u)≥0,for all 0≤u≤1. |
A natural choice for
q(u)=um−1,m>1, | (42) |
which states that the probability of a jump leaving one site increases with the cell density at that site [24,37].
Substituting (41) into the Master Equation (39) gives:
ddtui=qi−1(α+βi−1(τi−τi−1))ui−1+qi+1(α+βi+1(τi−τi+1))ui+1−qi(α+βi(τi+1−τi))ui−qi(α+βi(τi−1−τi))ui=α(qi−1ui−1+qi+1ui+1−2qiui)+βi−1qi−1(τi−τi−1)ui−1+βi+1qi+1(τi−τi+1)ui+1−βiqi(τi+1+τi−1−2τi)ui=α(qi−1ui−1+qi+1ui+1−2qiui)−βi+1qi+1ui+1(τi+1−τi)+βiqiui(τi−τi−1)−(βiqiui(τi+1−τi)−βi−1qi−1ui−1(τi−τi−1))=α(qi−1ui−1+qi+1ui+1−2qiui)−((βi+1qi+1ui+1+βiqiui)(τi+1−τi)−(βi−1qi−1ui−1+βiqiui)(τi−τi−1)). |
We set
∂u∂t=k(α∂2(q(u)u)∂x2−2∂∂x(βq(u)u∂τ∂x))+O(h2). |
By taking the limit of
∂u∂t=Du∂2(q(u)u)∂x2−∂∂x(βχ(v)q(u)u∂v∂x), |
where
Apart from that, we consider a modification of the Verhulst logistic growth term to model organ size evolution introduced by Blumberg [2] and Turner [41], which is called hyper-logistic function, accordingly
f(u)=ruδ(1−μu). |
Including cell kinetics and signal dynamics, we derive the resulting model for the cell movement
∂u∂t=DuΔ(q(u)u)⏟dispersion−χ0∇⋅(q(u)u∇v)⏟chemotaxis+μuδ(1−ru)⏟proliferation. |
Incorporating the kinetic equation of ECM and MDE, we arrive at a modified Chaplain and Lolas' chemotaxis model, see (3), where we assume the constants
The authors would like to express their sincere thanks to two anonymous referees for their valuable comments and suggestions, which led an important and significant improvement of the paper. The research of S. Ji is supported by NSFC Grant No. 11701184. The research of C. Jin was supported in part by NSFC grant No. 11471127, Guangdong Natural Science Funds for Distinguished Young Scholar Grant No. 2015A030306029, the Excellent Young Professors Program of Guangdong Province Grant No. HS2015007, and Special Support Program of Guangdong Province of China. The research of M. Mei was supported in part by NSERC Grant RGPIN 354724-16, and FRQNT Grant No. 192571. The research of J. Yin was supported in part by NSFC Grant No. 11771156.
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