For mechanical force to induce changes in cellular behaviors, two main processes are inevitable; perception of the force and response to it. Perception of mechanical force by cells, or mechanosensing, requires mechanical force-induced conformational changes in mechanosensors. For this, at least one end of the mechanosensors should be anchored to relatively fixed structures, such as extracellular matrices or the cytoskeletons, while the other end should be pulled along the direction of the mechanical force. Alternatively, mechanosensors may be positioned in lipid bilayers, so that conformational changes in the embedded sensors can be induced by mechanical force-driven tension in the lipid bilayer. Responses to mechanical force by cells, or mechanotransduction, require translation of such mechanical force-induced conformational changes into biochemical signaling. For this, protein-protein interactions or enzymatic activities of mechanosensors should be modulated in response to force-induced structural changes. In the last decade, several molecules that met the required criteria of mechanosensors have been identified and proven to directly sense mechanical force. The present review introduces examples of such mechanosensors and summarizes their mechanisms of action.
This study investigates focus and boundary effects on Korean nasal consonants and vowel nasalization. Under focus, nasal consonants lengthen in CVN# but shorten in #NVC, enhancing [nasal] vs [oral]. Vowels resist nasalization under focus, enhancing [oral]. Domain-initial nasal consonants denasalize, exercising no coarticulatory influence. Domain-final nasal consonants shorten counter to expectation, although vowel nasalization increases. Comparison with English data reveals similarities (focus-induced coarticulatory resistance) despite cross-linguistic differences in marking prominence, but it also suggests that prosodic-structural conditioning of non-contrastive vowel nasalization, albeit based on phonetic underpinnings of coarticulatory process, is fine-tuned in language-specific ways, resulting in cross-linguistic variation.
Cells can sense and respond to various mechanical stimuli from their surrounding environment. One of the explanations for mechanosensitivity, a lipidbilayer model, suggests that a stretch of the membrane induced by mechanical force alters the physical state of the lipid bilayer, driving mechanosensors to assume conformations better matched to the altered membrane. However, mechanosensors of this class are restricted to ion channels. Here, we reveal that integrin aIIbb3, a prototypic adhesion receptor, can be activated by various mechanical stimuli including stretch, shear stress, and osmotic pressure. The force-induced integrin activation was not dependent on its known intracellular activation signaling events and was even observed in reconstituted cell-free liposomes. Instead, these mechanical stimuli were found to alter the lipid embedding of the integrin b3 transmembrane domain (TMD) and subsequently weaken the aIIb-b3 TMD interaction, which results in activation of the receptor. Moreover, artificial modulation of the membrane curvature near integrin aIIbb3 can induce its activation in cells as well as in lipid nanodiscs, suggesting that physical deformation of the lipid bilayer, either by mechanical force or curvature, can induce integrin activation. Thus, our results establish the adhesion receptor as a bona fide mechanosensor that directly senses and responds to the force-modulated lipid environment. Furthermore, this study expands the lipidbilayer model by suggesting that the force-induced topological change of TMDs and subsequent alteration in the TMD interactome is a molecular basis of sensing mechanical force transmitted via the lipid bilayer. (D) The degrees of fibrinogen binding in THD-transfected cells. Error bars in (C) and (D) represent SD (n = 3). (E) Diagram of 33FLAG-aIIb(TMD-tail)-TAP and Tac-b3(TMD-tail). Abbreviation is as follows: TAP, tandem affinity purification. (F) CHO cells transfected with a and b TMD-tail constructs were stretched and maintained for 0, 1, or 5 min before their lysis. The TMD interaction was measured by detecting Tac-b3(TMD-tail) in precipitates of aIIb(TMD-tail)-TAP. Relative TMD interaction compared with nonstretched control is shown. *p < 0.05 (one-way ANOVA followed by Tukey multiple-comparison post hoc test). (G and H) Effect of Y747A mutation (G) or cytochalasin D (H) on stretch-induced disruption of aIIb-b3 TMD interaction. Error bars in (F)-(H) represent SE (n = 3). *p < 0.05, **p < 0.001, ***p < 0.0001. See also Figure S1.
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