کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
874353 | 910334 | 2007 | 11 صفحه PDF | دانلود رایگان |

It is now well established that cells can sense mechanical force, but the mechanisms by which force is transduced into a biochemical signal remain poorly understood. One example is the recruitment of vinculin to reinforce initial contacts between a cell and the extracellular matrix (ECM) due to tensile force. Talin, an essential linking protein in an initial contact, contains at least one vinculin-binding site (VBS) that is cryptic and inactive in the native state. The N-terminal five-helix bundle of talin rod is a stable structure with a known cryptic VBS1. The perturbation of this stable structure through elevated temperature or destabilizing mutation activates vinculin binding. Although the disruption of this subdomain by transmitted mechanical force is a potential cue for the force-induced focal adhesion strengthening, the molecular basis for this mechanism remains elusive. Here, molecular dynamics (MD) is employed to demonstrate a force-induced conformational change that exposes the cryptic vinculin-binding residues of VBS1 to solvent under applied force along a realistic pulling direction. VBS1 undergoes a rotation of 62.0±9.5° relative to its native state as its vinculin-binding residues are released from the tight hydrophobic core. Charged and polar residues on the VBS1 surface are the site of force transmission that strongly interact with an adjacent α-helix, and in effect, apply torque to the VBS1 to cause its rotation. Activation was observed with mean force of 13.2±8.0 pN during constant velocity simulation and with steady force greater than 18.0 pN.
Journal: Journal of Biomechanics - Volume 40, Issue 9, 2007, Pages 2096–2106