Year-end Sale % OFF 
Abstract
SummaryIn development, wound healing, and cancer metastasis, vertebrate cells move through 3D interstitial matrix, responding to chemical and physical guidance cues. Protrusion at the cell front has been extensively studied, but the retraction phase of the migration cycle is not well understood. Here, we show that fast-moving cells guided by matrix cues establish positive feedback control of rear retraction by sensing membrane tension. We reveal a mechanism of rear retraction in 3D matrix and durotaxis controlled by caveolae, which form in response to low membrane tension at the cell rear. Caveolae activate RhoA-ROCK1/PKN2 signaling via the RhoA guanidine nucleotide exchange factor (GEF) Ect2 to control local F-actin organization and contractility in this subcellular region and promote translocation of the cell rear. A positive feedback loop between cytoskeletal signaling and membrane tension leads to rapid retraction to complete the migration cycle in fast-moving cells, providing directional memory to drive persistent cell migration in complex matrices.
Highlights
Cell migration is a fundamental process that underpins development, health, and disease and is characterized by cycles of protrusion of the front and retraction of the rear (Ridley et al, 2003)
Rear Retraction in 3D Matrix and Durotaxis Is a Fast Dynamic Process Invasive cancer cells moving within fibrillar collagen and fibronectin 3D cell-derived matrix (CDM; Cukierman et al, 2001) followed the topology of fibrils with defined lamellipodial and filopodial protrusions at the cell front (Caswell and Zech, 2018; Paul et al, 2015) (Figures 1A and S1A), similar to that on 2D substrates
In the absence of a chemotactic gradient, we hypothesized that the direction of migration along matrix fibrils could be determined by the physical properties of the matrix
Summary
Cell migration is a fundamental process that underpins development, health, and disease and is characterized by cycles of protrusion of the front and retraction of the rear (Ridley et al, 2003). The plasma membrane is the physical barrier between intracellular and extracellular environments and plays an important role in cell migration by organizing signaling and exerting force (tension) on the underlying cytoskeleton (Diz-Munoz et al, 2013; Gauthier et al, 2012; Keren, 2011). Membrane tension has recently been shown to be a mechanical signal that regulates formation of focal adhesion complexes (Pontes et al, 2017) and the organization of actin networks (Mueller et al, 2017) at the leading edge of migrating cells on 2D substrates. Biophysical models have suggested that membrane tension at the cell rear might
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
