Recursive feedback between matrix dissipation and chemo-mechanical signaling drives oscillatory growth of cancer cell invadopodia

• Published in: Cell reports (Cambridge) Vol. 35; no. 4; p. 109047
• Main Authors: Gong, Ze, Wisdom, Katrina M., McEvoy, Eóin, Chang, Julie, Adebowale, Kolade, Price, Christopher C., Chaudhuri, Ovijit, Shenoy, Vivek B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.04.2021
• Subjects: Cell Movement; cyclic ratcheting; Extracellular Matrix - metabolism; Feedback; Humans; invadopodia; matrix plasticity; mechano-sensitive signaling pathways; myosin recruitment; oscillations; Podosomes - metabolism; Signal Transduction; timescales; invadopodia; mechano-sensitive signaling pathways; matrix plasticity; cyclic ratcheting; timescales; myosin recruitment; oscillations
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.109047

Most extracellular matrices (ECMs) are known to be dissipative, exhibiting viscoelastic and often plastic behaviors. However, the influence of dissipation, in particular mechanical plasticity in 3D confining microenvironments, on cell motility is not clear. In this study, we develop a chemo-mechanical model for dynamics of invadopodia, the protrusive structures that cancer cells use to facilitate invasion, by considering myosin recruitment, actin polymerization, matrix deformation, and mechano-sensitive signaling pathways. We demonstrate that matrix dissipation facilitates invadopodia growth by softening ECMs over repeated cycles, during which plastic deformation accumulates via cyclic ratcheting. Our model reveals that distinct protrusion patterns, oscillatory or monotonic, emerge from the interplay of timescales for polymerization-associated extension and myosin recruitment dynamics. Our model predicts the changes in invadopodia dynamics upon inhibition of myosin, adhesions, and the Rho-Rho-associated kinase (ROCK) pathway. Altogether, our work highlights the role of matrix plasticity in invadopodia dynamics and can help design dissipative biomaterials to modulate cancer cell motility. [Display omitted] •A chemo-mechanical model for invadopodia dynamics in 3D matrices is developed•Oscillations occur when timescales for extension and myosin dynamics are comparable•Matrix plastic strain accumulates by cyclic ratcheting during invadopodia growth•High matrix plasticity facilitates the oscillatory growth of invadopodia Gong et al. develop a chemo-mechanical model to predict the impact of matrix plasticity on invadopodia dynamics by considering myosin recruitment, actin polymerization, and mechano-sensitive signaling. The combined experiments and simulations show that invadopodia oscillate when timescales for extension and myosin dynamics are comparable, and high matrix plasticity facilitates the oscillations.