Nascent Focal Adhesions Are Responsible for the Generation of Strong Propulsive Forces in Migrating Fibroblasts

By K. Beningo, Micah Dembo, I. Kaverina, V. Small, Yu-li Wang. Journal of Cell Biology, 2001

762 citations recorded by the source corpus.

Fibroblast migration involves complex mechanical interactions with the underlying substrate. Although tight substrate contact at focal adhesions has been studied for decades, the role of focal adhesions in force transduction remains unclear. To address this question, we have mapped traction stress generated by fibroblasts expressing green fluorescent protein (GFP)-zyxin. Surprisingly, the overall distribution of focal adhesions only partially resembles the distribution of traction stress. In addition, detailed analysis reveals that the faint, small adhesions near the leading edge transmit strong propulsive tractions, whereas large, bright, mature focal adhesions exert weaker forces. This inverse relationship is unique to the leading edge of motile cells, and is not observed in the trailing edge or in stationary cells. Furthermore, time-lapse analysis indicates that traction forces decrease soon after the appearance of focal adhesions, whereas the size and zyxin concentration increase. As focal adhesions mature, changes in structure, protein content, or phosphorylation may cause the focal adhesion to change its function from the transmission of strong propulsive forces, to a passive anchorage device for maintaining a spread cell morphology.

Subfields: Atomic and Molecular Physics, and Optics, Cell Biology, Orthopedics and Sports Medicine

View Paper: https://www.semanticscholar.org/paper/4dcf1bafe14c926d5359c3f4c074cfea3f5b9c7b

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Citations in the corpus

Physical forces during collective cell migration (2009, background): “, it is now well established that a fundamental aspect of the motility mechanism is the transmission of contractile forces to the surrounding matrix at the cell’s leading and trailing edge”
Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion (2005, background): “…forces generated by small, nascent cell adhesions in lamellipodia are in fact greater than those generated by larger, more mature adhesions (Beningo et al., 2001; Munevar et al., 2001) are contradicted by those reporting that smaller focal complexes formed at the leading edge of a motile…”
Non-muscle myosin II takes centre stage in cell adhesion and migration (2009, neutral): “In addition, cells sense substrate pliability , in part through the activation of NM II by RLC phosphorylatio”
The relationship between force and focal complex development (2002, background): “However, it has also been reported that larger forces are supported at small nascent adhesions, and force decreases as the adhesions mature and increase in size (Pelham and Wang, 1999; Beningo et al., 2001).”
Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function (2003, background): “that generate transient pulses of propulsive traction forces during cell migratio”
Molecular complexity and dynamics of cell-matrix adhesions. (2001, background): “…compositions of focal complexes and focal contacts have not been quantitatively determined, although the former were reported to be enriched in activated αvβ3 integrin (Kiosses et al., 2001) and to apply stronger traction forces to the substrate during cell migration (Beningo et al., 2001).”
Myotubes differentiate optimally on substrates with tissue-like stiffness (2004, background): “This is consistent with stress fiber assembly in cells on very stiff gels and in cell types ranging from fibroblasts (Beningo et al., 2001) to SMCs (Gaudet et al.”
Transmembrane crosstalk between the extracellular matrix and the cytoskeleton (2001, background): “Nevertheless, seemingly similar early contacts have been reported to exert exceptionally strong forces that provide the main motive force for cell migratio”
The Actin Cytoskeleton and Actin-Based Motility (2018, background): “Counterintuitively, small and dynamic focal complexes associated with actin–myosin-II networks are more efficient in the generation of traction than large and stable focal adhesions (Beningo et al. 2001).”
MAP kinases and cell migration (2004, background): “, 2003) and evaluate effects on overall traction force production (Balaban et al., 2001; Beningo et al., 2001; Munevar et al., 2001; Tan et al., 2003).”
The physics of cancer: the role of physical interactions and mechanical forces in metastasis (2011, neutral): “Traction microscopy suggests that in 2D culture, a lamellipodium actively pulls the rest of the cell through nascent focal adhesions positioned at the edge of the lamellipodiu”
Mechanics, malignancy, and metastasis: The force journey of a tumor cell (2009, methodology): “These include methods for measuring mean rheological properties of whole cells, such as optical stretching [57–60], micropipette aspiration [61–65], traction force microscopy (TFM) [66–69], atomic force microscopy (AFM) [70–73], and magnetic twisting microrheometry [10, 74–77]; and microscale mechan”
Focal adhesion regulation of cell behavior. (2004, methodology): “The smaller complexes, which Beningo et al. [174] found to generate the largest amount of traction force, were likely smaller than 1 A m 2 [175].”
Integrin-mediated mechanotransduction (2016, background): “…no simple correlation between the adhesion size and the magnitude of the transmitted force (Oakes et al., 2012; Schiller et al., 2013), Integrin-mediated mechanotransduction • Sun et al. 447 as small NAs may also transmit forces that are high enough to drive cell migration (Beningo et al., 2001).”