AsianScientist (Aug. 29, 2014) – Scientists have demonstrated a molecular mechanism that could explain how the mechanical forces experienced by cells are translated into biochemical signals. This research, published in Nature Communications, has important implications on our understanding of biological processes such as cell-cell communication and tumor progression.
The correct response of cells to mechanical stimulation is required for development and homeostasis; dysregulation in mechanosensing can lead to diseases such as muscular dystrophy and cancer. In particular, the cell adhesion protein α-catenin is known to be important for mechanosensing through its interactions with the cytoplasmic protein, vinculin.
Although it has long been thought that the application of force causes α-catenin to unfold, allowing vinculin to bind and effect downstream changes, this hypothesis has never been proven experimentally.
In the present study, a team of researchers led by associate professor Yan Jie from the Mechanobiology Institute at the University of Singapore has demonstrated for the first time that α-catenin acts as a force-dependent molecular switch, thereby explaining local mechanosensing at cell-cell junctions.
In experiments using magnetic tweezers, where the extension of α-catenin in response to controlled force was quantified, they showed that the application of ~5 pN of force caused a partial unfolding of α-catenin, exposing the vinculin binding site. Once vinculin binds to α-catenin, it locks α-catenin in an open conformation, only releasing α-catenin when a higher force of about ~30 pN was applied.
The authors suggest that locking α-catenin in an open conformation allows cell adhesion to be regulated by changes in mechanical force experienced by the cell. Further studies in cells are required the clarify the details of this mechanism and to address whether it is unique to cell-cell junctions or can be used to explain general principles of mechanosensing.
The article can be found at: Yao et al. (2014) Force-Dependent Conformational Switch of α-catenin Controls Vinculin Binding.
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Copyright: Asian Scientist Magazine; Photo: Mechanobiology Institute.
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