Force Fluctuations within Focal Adhesions Mediate ECM-Rigidity Sensing to Guide Directed Cell Migration

By Sergey V Plotnikov, A. M. Pasapera, Benedikt Sabass, Clare M. Waterman. Cell, 2012

802 citations recorded by the source corpus.

Summary Cell migration toward areas of higher extracellular matrix (ECM) rigidity via a process called “durotaxis” is thought to contribute to development, immune response, and cancer metastasis. To understand how cells sample ECM rigidity to guide durotaxis, we characterized cell-generated forces on the nanoscale within single mature integrin-based focal adhesions (FAs). We found that individual FAs act autonomously, exhibiting either stable or dynamically fluctuating (“tugging”) traction. We show that a FAK/phosphopaxillin/vinculin pathway is essential for high FA traction and to enable tugging FA traction over a broad range of ECM rigidities. We show that tugging FA traction is dispensable for FA maturation, chemotaxis, and haptotaxis but is critical to direct cell migration toward rigid ECM. We conclude that individual FAs dynamically sample rigidity by applying fluctuating pulling forces to the ECM to act as sensors to guide durotaxis, and that FAK/phosphopaxillin/vinculin signaling defines the rigidity range over which this dynamic sensing process operates.

Subfields: Biomedical Engineering, Cell Biology, Cellular and Molecular Neuroscience

View Paper: https://www.semanticscholar.org/paper/e3def50dab27627c9649f31b0f595cfa1f753a79

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In Biomedical Engineering

1. Ulrich S. Schwarz
2. Shmuel Safran

In Cell Biology

1. Ulrich S. Schwarz
2. Shmuel Safran
3. R. Fässler

Citations in the corpus

• Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. (2014, neutral): “from cytoskeletal contractility (discussed below; [13, 76]).”
• Physics of adherent cells (2013, background): “Because focal adhesions are connected to the matrix, these forces are transmitted to the substrate and can be measured there with traction force microscopy on flat elastic substrates (Dembo and Wang, 1999; Butler et al., 2002; Schwarz et al., 2002; Sabass et al., 2008; Plotnikov et al., 2012; Legant”
• Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression (2015, background): “A FA complex in a cell functions as a mechanosensor that generates a fluctuating force to pull the ECM, thereby directing cells to migrate to an area with greater ECM stiffness.(12) These findings suggest that ECM stiffness is able to regulate FAK activity to trigger subsequent activation of signal ”
• Integrin-mediated mechanotransduction (2016, background): “The consequences of mechanical stress on the nucleus, similar to the mechanical stress in FAs, are changes in protein localization, protein conformation, and complex formation (Poh et al., 2012; Swift et al., 2013; Guilluy et al., 2014; Le et al., 2016).”