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Hele–Shaw Limit for a System of Two Reaction-(Cross-)Diffusion Equations for Living Tissues

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Abstract

Multiphase mechanical models are now commonly used to describe living tissues including tumour growth. The specific model we study here consists of two equations of mixed parabolic and hyperbolic type which extend the standard compressible porous medium equation, including cross-reaction terms. We study the incompressible limit, when the pressure becomes stiff, which generates a free boundary problem. We establish the complementarity relation and also a phase-segregation result. Several major mathematical difficulties arise in the two species case. Firstly, the system structure makes comparison principles fail. Secondly, segregation and internal layers limit the regularity available on some quantities to BV. Thirdly, the Aronson–Bénilan estimates cannot be established in our context. We are led, as it is classical, to add correction terms. This procedure requires technical manipulations based on BV estimates only valid in one space dimension. Another novelty is to establish an \(L^1\) version in place of the standard upper bound.

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References

  1. Aronson, D.G., Bénilan, P.: Régularité des solutions de l’équation des milieux poreux dans \({\mathbb{R}}^n\). CR Acad. Sci. Paris Sér. AB288(2), A103–A105, 1979

    MATH  Google Scholar 

  2. Bertsch, M., Dal Passo, R., Mimura, M.: A free boundary problem arising in a simplified tumour growth model of contact inhibition. Interfaces Free Bound. 12(2), 235–250, 2010

    Article  MathSciNet  Google Scholar 

  3. Bertsch, M., Gurtin, M.E., Hilhorst, D.: On interacting populations that disperse to avoid crowding: the case of equal dispersal velocities. Nonlinear Anal. Theory Methods Appl. 11(4), 493–499, 1987

    Article  MathSciNet  Google Scholar 

  4. Bertsch, M., Hilhorst, D., Izuhara, H., Mimura, M.: A nonlinear parabolic–hyperbolic system for contact inhibition of cell-growth. Differ. Equ. Appl. 4(1), 137–157, 2012

    MathSciNet  MATH  Google Scholar 

  5. Bresch, D., Colin, T., Grenier, E., Ribba, B., Saut, O.: Computational modeling of solid tumor growth: the avascular stage. SIAM J. Sci. Comput. 32(4), 2321–2344, 2010

    Article  MathSciNet  Google Scholar 

  6. Bris, C.L., Lions, P.-L.: Existence and uniqueness of solutions to Fokker–Planck type equations with irregular coefficients. Commun. Partial Differ. Equ. 33(7), 1272–1317, 2008

    Article  MathSciNet  Google Scholar 

  7. Busenberg, S.N., Travis, C.C.: Epidemic models with spatial spread due to population migration. J. Math. Biol. 16(2), 181–198, 1983

    Article  MathSciNet  Google Scholar 

  8. Byrne, H.M., Drasdo, D.: Individual-based and continuum models of growing cell populations: a comparison. Math. Med. Biol. 58(4–5), 657–687, 2003

    MathSciNet  MATH  Google Scholar 

  9. Carrillo, J.A., Fagioli, S., Santambrogio, F., Schmidtchen, M.: Splitting schemes and segregation in reaction cross-diffusion systems. SIAM J. Math. Anal. 50(5), 5695–5718, 2018

    Article  MathSciNet  Google Scholar 

  10. Craig, K., Kim, I., Yao, Y.: Congested aggregation via Newtonian interaction. Arch. Ration. Mech. Anal. 227(1), 1–67, 2018

    Article  MathSciNet  Google Scholar 

  11. Dambrine, J., Meunier, N., Maury, B., Roudneff-Chupin, A.: A congestion model for cell migration. Commun. Pure Appl. Anal. 11(1), 243–260, 2012

    Article  MathSciNet  Google Scholar 

  12. Degond, P., Hecht, S., Vauchelet, N.: Incompressible limit of a continuum model of tissue growth for two cell populations. arXiv:1809.05442, 2018

  13. Gurtin, M.E., Pipkin, A.C.: A note on interacting populations that disperse to avoid crowding. Quart. Appl. Math. 42, 87–94, 1984

    Article  MathSciNet  Google Scholar 

  14. Gwiazda, P., Perthame, B., Świerczewska-Gwiazda, A.: A two species hyperbolic–parabolic model of tissue growth. arXiv:1809.01867, 2018

  15. Hecht, S., Vauchelet, N.: Incompressible limit of a mechanical model for tissue growth with non-overlapping constraint. Commun. Math. Sci. 15(7), 1913, 2017

    Article  MathSciNet  Google Scholar 

  16. Kim, I., Požár, N.: Porous medium equation to Hele–Shaw flow with general initial density. Trans. Am. Math. Soc. 370(2), 873–909, 2018

    Article  MathSciNet  Google Scholar 

  17. Kim, I., Turanova, O.: Uniform convergence for the incompressible limit of a tumor growth model. Ann. Inst. H. Poincaré Anal. Non Linéaire35(5), 1321–1354, 2018

    Article  ADS  MathSciNet  Google Scholar 

  18. Kim, I.C., Perthame, B., Souganidis, P.E.: Free boundary problems for tumor growth: a viscosity solutions approach. Nonlinear Anal. 138, 207–228, 2016

    Article  MathSciNet  Google Scholar 

  19. Lorenzi, T., Lorz, A., Perthame, B.: On interfaces between cell populations with different mobilities. Kinet. Relat. Models10(1), 299–311, 2017

    Article  MathSciNet  Google Scholar 

  20. Lowengrub, J.S., Frieboes, H.B., Jin, F., Chuang, Y.-L., Li, X., Macklin, P., Wise, S.M., Cristini, V.: Nonlinear modelling of cancer: bridging the gap between cells and tumours. Nonlinearity23(1), R1–R91, 2010

    Article  MathSciNet  Google Scholar 

  21. Lu, P., Ni, L., Vázquez, J.-L., Villani, C.: Local Aronson–Bénilan estimates and entropy formulae for porous medium and fast diffusion equations on manifolds. J. Math. Pures Appl. (9)91(1), 1–19, 2009

    Article  MathSciNet  Google Scholar 

  22. Maury, B., Roudneff-Chupin, A., Santambrogio, F.: A macroscopic crowd motion model of gradient flow type. Math. Models Methods Appl. Sci. 20(10), 1787–1821, 2010

    Article  MathSciNet  Google Scholar 

  23. Maury, B., Roudneff-Chupin, A., Santambrogio, F.: Congestion-driven dendritic growth. Discrete Contin. Dyn. Syst. 34(4), 1575–1604, 2014

    Article  MathSciNet  Google Scholar 

  24. Maury, B., Roudneff-Chupin, A., Santambrogio, F., Venel, J.: Handling congestion in crowd motion modeling. Netw. Heterog. Media6(3), 485–519, 2011

    Article  MathSciNet  Google Scholar 

  25. Mellet, A., Perthame, B., Quirós, F.: A Hele–Shaw problem for tumor growth. J. Funct. Anal. 273(10), 3061–3093, 2017

    Article  MathSciNet  Google Scholar 

  26. Mészáros, A.R., Santambrogio, F.: Advection–diffusion equations with densityconstraints. Anal. PDE9(3), 615–644, 2016

    Article  MathSciNet  Google Scholar 

  27. Motsch, S., Peurichard, D.: From short-range repulsion to Hele–Shaw problem in a model of tumor growth. J. Math. Biol. 76(1–2), 205–234, 2018

    Article  MathSciNet  Google Scholar 

  28. Perthame, B., Quirós, F., Tang, M., Vauchelet, N.: Derivation of a Hele–Shaw type system from a cell model with active motion. Interfaces Free Bound. 16, 489–508, 2014

    Article  MathSciNet  Google Scholar 

  29. Perthame, B., Quirós, F., Vázquez, J.L.: The Hele–Shaw asymptotics for mechanical models of tumor growth. Arch. Ration. Mech. Anal. 212(1), 93–127, 2014

    Article  MathSciNet  Google Scholar 

  30. Preziosi, L.: A review of mathematical models for the formation of vascular networks. J. Theor. Biol. 333, 174–209, 2012

    MathSciNet  MATH  Google Scholar 

  31. Ranft, J., Basana, M., Elgeti, J., Joanny, J.-F., Prost, J., Jülicher, F.: Fluidization of tissues by cell division and apoptosis. Natl. Acad. Sci. USA49, 657–687, 2010

    Google Scholar 

  32. Roose, T., Chapman, S.J., Maini, P.K.: Mathematical models of avascular tumour growth: a review. SIAM Rev. 49(2), 179–208, 2007

    Article  ADS  MathSciNet  Google Scholar 

  33. Vázquez, J.L.: The Porous Medium Equation: Mathematical Theory. Oxford University Press, Oxford 2007

    MATH  Google Scholar 

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Acknowledgements

F.B. and B.P. have received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 740623). M.S. acknowledges the kind invitation to LJLL funded by the previous grant. Furthermore, M.S. received funding for two research visits from the Doris Chen Mobility Award awarded by Imperial College London. C.P. acknowledges support from the Swedish Foundation of Strategic Research Grant AM13-004.

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Correspondence to Camille Pouchol.

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Appendix A. Energy

Appendix A. Energy

Proposition 5

Let \(H_1(p) := \int _0^{p} F(z) \, \mathrm {d}z\) and \(H_2(p) := \int _0^{p} G(z) \, \mathrm {d}z\) for \(p \geqq 0\). Then, the energy

$$\begin{aligned} {\mathcal {E}}(t) := \int _\Omega \left( \frac{1}{2}\left| \frac{\partial p_{\gamma , \varepsilon }}{\partial x} \right| ^2 - c^{(1)}_{\gamma ,\varepsilon } H_1(p_{\gamma , \varepsilon }) - c^{(2)}_{\gamma ,\varepsilon } H_2(p_{\gamma , \varepsilon })\right) \mathrm {d}x \end{aligned}$$

is such that, for a constant C independent of \(\gamma \) and \(\varepsilon \),

$$\begin{aligned} {\mathcal {E}}'(t) + \gamma \int _{\Omega } p_{\gamma ,\varepsilon } w_{\gamma ,\varepsilon } ^2 \mathrm {d}x \leqq C. \end{aligned}$$
(44)

Proof

Consider the equation for the pressure (16) and multiply by \(- \tfrac{\partial ^2 p_\gamma }{\partial x^2}\). Integration by parts yields

$$\begin{aligned} \frac{1}{2}\frac{\mathrm {d}}{\mathrm {d}t}\int _\Omega \left| \dfrac{\partial p_\gamma }{\partial x}\right| ^2 \mathrm {d}x +\gamma \int _\Omega p_\gamma \left| \dfrac{\partial ^2 p_\gamma }{\partial x^2}\right| ^2 \mathrm {d}x + \gamma \int _\Omega p_\gamma \dfrac{\partial ^2 p_\gamma }{\partial x^2}R \, \mathrm {d}x = 0. \end{aligned}$$
(45)

Moreover, using the equations for \(c_\gamma ^{(1)}\) and \(c_\gamma ^{(2)}\), we compute

$$\begin{aligned} \begin{aligned}&\frac{\partial \left( c_\gamma ^{(1)}H_1(p_\gamma ) \right) }{\partial t}\\&\quad = H_1(p_\gamma ) \left( \frac{\partial c_\gamma ^{(1)}}{\partial x}\dfrac{\partial p_\gamma }{\partial x}+ c_\gamma ^{(1)}F_1(p_\gamma ) + c_\gamma ^{(2)}G_1(p_\gamma ) \right. \\&\qquad \left. - (c_\gamma ^{(1)})^2F(p_\gamma ) - c_\gamma ^{(1)}\,c_\gamma ^{(2)}G(p_\gamma )\right) \\&\qquad + c_\gamma ^{(1)}F(p_\gamma ) \left[ \left| \dfrac{\partial p_\gamma }{\partial x}\right| ^2 + \gamma p_\gamma w_\gamma \right] , \end{aligned} \end{aligned}$$
(46)

and

$$\begin{aligned} \begin{aligned}&\frac{\partial \left( c_\gamma ^{(2)}H_2(p_\gamma ) \right) }{\partial t}\\&\quad = H_2(p_\gamma ) \left( \frac{\partial c_\gamma ^{(2)}}{\partial x}\dfrac{\partial p_\gamma }{\partial x}+ c_\gamma ^{(1)}F_2(p_\gamma ) + c_\gamma ^{(2)}G_2(p_\gamma )\right. \\&\left. \qquad - (c_\gamma ^{(2)})^2\,G(p_\gamma ) - c_\gamma ^{(1)}\, c_\gamma ^{(2)}F(p_\gamma )\right) \\&\qquad + c_\gamma ^{(2)}G(p_\gamma ) \left[ \left| \dfrac{\partial p_\gamma }{\partial x}\right| ^2 + \gamma p_\gamma w_\gamma \right] . \end{aligned} \end{aligned}$$
(47)

Summing (45), (46) and (47), and using the uniform bounds for \(c_\gamma ^{(1)}\), \(c_\gamma ^{(2)}\) and the reaction terms, we get

$$\begin{aligned}&\frac{\mathrm {d}}{\mathrm {d}t}\int _\Omega \bigg ( \frac{1}{2} \left| \dfrac{\partial p_\gamma }{\partial x}\right| ^2 - c_\gamma ^{(1)}H_1(p_\gamma ) - c_\gamma ^{(2)}H_2(p_\gamma ) \bigg ) \mathrm {d}x + \gamma \int _{\Omega } p_\gamma w_\gamma ^2 \mathrm {d}x \leqq \\&\quad C \int _{\Omega } \left[ \left| \dfrac{\partial p_\gamma }{\partial x}\right| ^2 + \left| \dfrac{\partial p_\gamma }{\partial x}\right| \left( \left| \frac{\partial c_\gamma ^{(1)}}{\partial x}\right| + \left| \frac{\partial c_\gamma ^{(2)}}{\partial x}\right| \right) \right] \mathrm {d}x. \end{aligned}$$

Theorem 3.1, together with the Hölder inequality and the Sobolev embeddings, yield the desired bound (44). \(\quad \square \)

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Bubba, F., Perthame, B., Pouchol, C. et al. Hele–Shaw Limit for a System of Two Reaction-(Cross-)Diffusion Equations for Living Tissues. Arch Rational Mech Anal 236, 735–766 (2020). https://doi.org/10.1007/s00205-019-01479-1

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