Cell-Substrate Patterns Driven by Curvature-Sensitive Actin Polymerization: Waves and Podosomes

Abstract

Cells adhered to an external solid substrate are observed to exhibit rich dynamics of actin structures on the basal membrane, which are distinct from those observed on the dorsal (free) membrane. Here we explore the dynamics of curved membrane proteins, or protein complexes, that recruit actin polymerization when the membrane is confined by the solid substrate. Such curved proteins can induce the spontaneous formation of membrane protrusions on the dorsal side of cells. However, on the basal side of the cells, such protrusions can only extend as far as the solid substrate and this constraint can convert such protrusions into propagating wave-like structures. We also demonstrate that adhesion molecules can stabilize localized protrusions that resemble some features of podosomes. This coupling of curvature and actin forces may underlie the differences in the observed actin-membrane dynamics between the basal and dorsal sides of adhered cells.

Chemo-mechanical diffusion waves explain collective dynamics of immune cell podosomes

“…More importantly, our study demonstrates that the Rho-ROCK pathway is a critical mechanosensitive mediator of the vertical oscillations of podosomes. This mechanosensitive signaling feedback has not been emphasized in previous theoretical studies on dynamics of individual podosomes 6 , 7 , 25 , 26 . Here, our model predicts that the weak mechanosensitive feedback Γ due to this pathway inhibits podosome oscillations, which has been validated by our experiments using Y27632 treatment.…”

From actin waves to mechanism and back: How theory aids biological understanding

“…Alternatively, negative feedback can also form from a mixture of convex and concave proteins that accumulate in regions where the membrane retracts inward ( Peleg et al, 2011 ). The negative feedback can even arise from external rigid confinement ( Naoz and Gov, 2020 ), which is relevant for actin waves on the ventral cell side, facing the substrate. Finally, a mechano-chemical feedback through Ca 2+ -ion flux can also lead to waves and oscillations ( Veksler and Gov, 2009 ).…”

Why a Large-Scale Mode Can Be Essential for Understanding Intracellular Actin Waves

“…Another group of biophysics-based models contains curved membrane proteins that nucleate the cortical actin polymerization [ 69 , 70 , 71 , 72 , 73 ]. In these models, the curved proteins flow/adsorb to the membrane regions that have a curvature similar to their intrinsic shape, and their concentration is therefore affected by the membrane deformations that are induced by the forces exerted by the actin cytoskeleton.…”