journal article·2008-05

Modeling mechanosensing and its effect on the migration and proliferation of adherent cells

Pedro Moreo, José Manuel García-Aznar, Manuel Doblaré

Acta Biomaterialia· Volume 4· Issue 3
Publisher page

Abstract

The behavior of normal adherent cells is influenced by the stiffness of the substrate they are anchored to. Cells are able to detect substrate mechanical properties by actively generating contractile forces and use this information to migrate and proliferate. In particular, the speed and direction of cell crawling, as well as the rate of cell proliferation, vary with the substrate compliance and prestrain. In this work, we present an active mechanosensing model based on an extension of the classical Hill's model for skeletal muscle behavior. We also propose a thermodynamical approach to model cell migration regulated by mechanical stimuli and a proliferation theory also depending on the mechanical environment. These contributions give rise to a conceptually simple mathematical formulation with a straightforward and inexpensive computational implementation, yielding results consistent with numerous experiments. The model can be a useful tool for practical applications in biology and medicine in situations where cell-substrate interaction as well as substrate mechanical behavior play an important role, such as the design of tissue engineering applications.
Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

OpenAlex topics: Cellular Mechanics and Interactions · thermodynamics and calorimetric analyses · 3D Printing in Biomedical Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (42)

Show source-provided references
1. Cell migration research is on the move10.1126/science.295.5555.606 ↗
2. Cell migration: a physically integrated molecular process10.1016/S0092-8674(00)81280-5 ↗
3. Mechanical characterization of collagen–glycosaminoglycan scaffolds10.1016/j.actbio.2006.12.009 ↗
4. Directed movement of vascular smooth muscle cells on gradient-compliant hydrogels10.1021/la026403p ↗
5. Cell locomotion and focal adhesions are regulated by substrate flexibility10.1073/pnas.94.25.13661 ↗
6. Substrate compliance versus ligand density in cell on gel responses10.1016/S0006-3495(04)74140-5 ↗
7. Physical determinants of cell organization in soft media10.1016/j.medengphy.2005.04.007 ↗
8. Cell adaptation to a physiologically relevant ecm mimic with different viscoelastic properties10.1016/j.biomaterials.2006.09.038 ↗
9. Tissue cells feel and respond to the stiffness of their substrate10.1126/science.1116995 ↗
10. Adhesion-dependent cell mechanosensitivity10.1146/annurev.cellbio.19.111301.153011 ↗
11. Molecular complexity and dynamics of cell–matrix adhesions10.1242/jcs.114.20.3583 ↗
12. Is the mechanical activity of epithelial cells controlled by deformations or forces?10.1529/biophysj.105.071217 ↗
13. Cell movement is guided by the rigidity of the substrate10.1016/S0006-3495(00)76279-5 ↗
14. Taking cell–matrix adhesions to the third dimension10.1126/science.1064829 ↗
15. Tensile stress simulates microtubule outgrowth in living cells10.1242/jcs.115.11.2283 ↗
16. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and rock-independent mechanism10.1083/jcb.153.6.1175 ↗
17. Systems biology: a brief overview10.1126/science.1069492 ↗
18. The Turing model comes of molecular age10.1126/science.1136396 ↗
19. Biomechanics and biophysics of cancer cells10.1016/j.actbio.2007.04.002 ↗
20. Cell organization in soft media due to active mechanosensing10.1073/pnas.1233544100 ↗
21. Cell mechanosensitivity controls the anisotropy of focal adhesions10.1073/pnas.0403539101 ↗
22. Focal adhesions as mechanosensors: the two-spring model10.1016/j.biosystems.2005.05.019 ↗
23. Mathematical model for the effects of adhesion and mechanics on cell migration speed10.1016/S0006-3495(91)82027-6 ↗
24. Computational model for cell migration in three-dimensional matrices10.1529/biophysj.105.060723 ↗
25. The heat of shortening and the dynamic constants of muscle10.1098/rspb.1938.0050 ↗
26. Tensegrity. I. Cell structure and hierarchical systems biology10.1242/jcs.00359 ↗
27. Timoshenko · 1970
28. The myosin swinging cross-bridge model10.1038/35073086 ↗
29. Length dependence of active force production in skeletal muscle10.1152/jappl.1999.86.5.1445 ↗
30. Critical conditions for pattern formation and in vitro tubulogenesis driven by cellular traction fields10.1016/j.jtbi.2003.10.015 ↗
31. Mechanical aspects of mesenchymal morphogenesis
32. Marsden · 1994
33. On the numerical modelling of growth, differentiation and damage in structural living tissues
34. Murray · 2005
35. Tension-dependent collective cell movements in the early gastrula ectoderm of xenopus laevis embryos10.1007/s004270050015 ↗
36. Dynamic imaging of neutrophil migration in three dimensions: mechanical interactions between cells and matrix10.1002/jlb.61.2.188 ↗
37. Temporal variations in cell migration and traction during fibroblast-mediated gel compaction10.1016/S0006-3495(03)75135-2 ↗
38. Anisotropic mechanosensing by mesenchymal stem cells10.1073/pnas.0604182103 ↗
39. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion10.1002/cm.20041 ↗
40. Mechanical modelling of cell/ecm and cell/cell interactions during the contraction of a fibroblast-populated collagen microsphere: theory and model simulation10.1016/j.jbiomech.2004.01.028 ↗
41. Mechanical models for living cells – a review10.1016/j.jbiomech.2004.12.008 ↗
42. Cell type-specific response to growth on soft materials10.1152/japplphysiol.01121.2004 ↗