From Single Molecules to Living Cells: Nanomechanical Measurements of Cell Adhesion Export

@article{citeulike:3689958, abstract = {Abstract  This review highlights complementary force probe techniques and illustrates how these approaches provide different, but complementary insight into molecular mechanisms of cell adhesion. As a model system, we focus on classical cadherins, which mediate cell–cell adhesion in all solid tissues. The experimental approaches described probe cadherin binding from single molecules to cells, and quantify the kinetics, energetics, and mechanical strengths of cadherin-mediated adhesive contacts. The cumulative findings of these complementary studies reveal complexities of the cadherin binding mechanism, and quantify relevant bond parameters. Importantly these different approaches demonstrate how the strengths and kinetics of cadherin bonds at the single molecule level govern the initial dynamics of adhesion between living cells. The findings also exemplify the capacity of these different force probe techniques to identify novel properties of molecular interactions governing biological adhesion.}, author = {Leckband, Deborah}, citeulike-article-id = {3689958}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s12195-008-0029-3}, citeulike-linkout-1 = {http://www.springerlink.com/content/x2x774q4753t7205}, comment = {I like this review because it illustrated how various experimental techniques can complement each other to provide a more complete and accurate picture of cell-adhesion at the molecular level. The example used is classical cadherins (5 EC domains), which was formerly known to adhere via their first Extracellular (EC) domains in what is called the strand-exchange model. This simple association model predicts a single exponential increase of the binding probability to a saturating value of 0.4. However, use of micropipette manipulations indicated that the binding probability should be biphasic, with a short initial increase to 0.4 (weak binding) followed by another increase to 0.6-0.8 (stronger binding). Biomembrane force probe which can measure the rupture force of each bond could single out force peaks corresponding to weak (by EC 1-2 domains) and strong bonds (EC 3-5). The technique also showed a time transition from weak bonds to strong bonds. Finally, Surface Force Apparatus which could quantify how the adhesion energy varies with intersurface separation (with a spatial resolution of +/- 0.1 nm!). This energy is determined from the pull-off force. By changing the separation of cadherin monomers on two opposing surfaces, it was discovered that there are three specific distances with strong adhesion, found to correspond to EC1:EC1, EC1-3:EC1-3 and full domain overlaps with the use of deletion mutants. Thus, we now know that initial weak association requires domain EC1 while additional stronger bonds requires EC3. }, doi = {10.1007/s12195-008-0029-3}, journal = {Cellular and Molecular Bioengineering}, keywords = {cell-adhesion, single-molecule-methods}, month = {December}, number = {4}, pages = {312--326}, posted-at = {2009-01-06 03:30:43}, priority = {3}, title = {From Single Molecules to Living Cells: Nanomechanical Measurements of Cell Adhesion}, url = {http://dx.doi.org/10.1007/s12195-008-0029-3}, volume = {1}, year = {2008} }

TY - JOUR ID - citeulike:3689958 L3 - citeulike-article-id:3689958 N2 - Abstract  This review highlights complementary force probe techniques and illustrates how these approaches provide different, but complementary insight into molecular mechanisms of cell adhesion. As a model system, we focus on classical cadherins, which mediate cell–cell adhesion in all solid tissues. The experimental approaches described probe cadherin binding from single molecules to cells, and quantify the kinetics, energetics, and mechanical strengths of cadherin-mediated adhesive contacts. The cumulative findings of these complementary studies reveal complexities of the cadherin binding mechanism, and quantify relevant bond parameters. Importantly these different approaches demonstrate how the strengths and kinetics of cadherin bonds at the single molecule level govern the initial dynamics of adhesion between living cells. The findings also exemplify the capacity of these different force probe techniques to identify novel properties of molecular interactions governing biological adhesion. IS - 4 JF - Cellular and Molecular Bioengineering EP - 326 TI - From Single Molecules to Living Cells: Nanomechanical Measurements of Cell Adhesion VL - 1 SP - 312 KW - cell-adhesion KW - single-molecule-methods N1 - I like this review because it illustrated how various experimental techniques can complement each other to provide a more complete and accurate picture of cell-adhesion at the molecular level. The example used is classical cadherins (5 EC domains), which was formerly known to adhere via their first Extracellular (EC) domains in what is called the strand-exchange model. This simple association model predicts a single exponential increase of the binding probability to a saturating value of 0.4. However, use of micropipette manipulations indicated that the binding probability should be biphasic, with a short initial increase to 0.4 (weak binding) followed by another increase to 0.6-0.8 (stronger binding). Biomembrane force probe which can measure the rupture force of each bond could single out force peaks corresponding to weak (by EC 1-2 domains) and strong bonds (EC 3-5). The technique also showed a time transition from weak bonds to strong bonds. Finally, Surface Force Apparatus which could quantify how the adhesion energy varies with intersurface separation (with a spatial resolution of +/- 0.1 nm!). This energy is determined from the pull-off force. By changing the separation of cadherin monomers on two opposing surfaces, it was discovered that there are three specific distances with strong adhesion, found to correspond to EC1:EC1, EC1-3:EC1-3 and full domain overlaps with the use of deletion mutants. Thus, we now know that initial weak association requires domain EC1 while additional stronger bonds requires EC3. AU - Leckband, Deborah PY - 2008/12// UR - http://dx.doi.org/10.1007/s12195-008-0029-3 ER -