Refine
Language
- English (2)
Has Fulltext
- yes (2)
Is part of the Bibliography
- yes (2)
Keywords
- RhoGTPase (1)
- actin dynamics (1)
- caveolae (1)
- cell invasion (1)
- cell migration (1)
- cytochalasin D (1)
- cytoskeleton (1)
- durotaxis (1)
- extracellular matrix (1)
- membrane tension (1)
Scientific Unit
Summary In 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.
The study of the actin cytoskeleton and related cellular processes requires tools to specifically interfere withactin dynamics in living cell cultures, ideally with spatiotemporal control and compatible with real time imaging.A phototriggerable derivative of the actin disruptor Cytochalasin D (CytoD) is described and tested here. Itincludes a nitroveratryloxycarbonyl (Nvoc) photoremovable protecting group (PPG) at the hydroxyl group atC7 of CytoD. The attachment of the PPG renders Nvoc-CytoD temporarily inactive, and enables light-doseddelivery of the active drug CytoD to living cells. This article presents the full structural and physicochemicalcharacterization, the toxicity analysis. It is complemented with biological tests to show the time scales(seconds) and spatial resolution (cellular level) achievable with a UV source in a regular microscopy setup.
