Forced-rupture of cell-adhesion complexes reveals abrupt switch between two brittle states
| Autor: | Ngo Minh Toan, Dave Thirumalai |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Materials science Kinetics General Physics and Astronomy FOS: Physical sciences Thermodynamics 010402 general chemistry Ligands Microscopy Atomic Force Molecular physics 01 natural sciences Reaction coordinate Physical Phenomena 03 medical and health sciences Special Topic: Single Molecule Biophysics Coordination Complexes Cell Adhesion Molecule Magnesium Physics - Biological Physics Physical and Theoretical Chemistry Condensed Matter - Statistical Mechanics 030304 developmental biology Ions 0303 health sciences Statistical Mechanics (cond-mat.stat-mech) Force spectroscopy Biomolecules (q-bio.BM) Adhesion Ligand (biochemistry) Transition state Lymphocyte Function-Associated Antigen-1 0104 chemical sciences 030104 developmental biology Quantitative Biology - Biomolecules Biological Physics (physics.bio-ph) FOS: Biological sciences Constant (mathematics) |
| Zdroj: | The Journal of chemical physics. 148(12) |
| ISSN: | 1089-7690 |
| Popis: | Cell adhesion complexes (CACs), which are activated by ligand binding, play key roles in many cellular functions ranging from cell cycle regulation to mediation of cell extracellular matrix adhesion. Inspired by single molecule pulling experiments on leukocyte function-associated antigen-1 (LFA-1), expressed in T-cells, bound to intercellular adhesion molecules (ICAM), we performed constant loading rate ($r_f$) and constant force ($F$) simulations using the Self-Organized Polymer (SOP) model to describe the mechanism of ligand rupture from CACs. The simulations reproduce the major experimental finding on the kinetics of the rupture process, namely, the dependence of the most probable rupture forces ($f^*$s) on $\ln r_f$ ($r_f$ is the loading rate) exhibits two distinct linear regimes. The first, at low $r_f$, has a shallow slope whereas the slope at high $r_f$ is much larger, especially for LFA-1/ICAM-1 complex with the transition between the two occurring over a narrow $r_f$ range. Locations of the two transition states (TSs), extracted from the simulations show an abrupt change from a high value at low $r_f$ or $F$ to a low value at high $r_f$ or $F$. The unusual behavior in which the CACs switch from one brittle (TS position is a constant over a range of forces) state to another brittle state is not found in forced-rupture in other protein complexes. We explain this novel behavior by constructing the free energy profiles, $F(\Lambda)$s, as a function of a collective reaction coordinate ($\Lambda$), involving many key charged residues and a critical metal ion. The TS positions in F($\Lambda) change abruptly at a critical force, demonstrating that it, rather than the molecular extension is a good reaction coordinate. We reveal a new mechanism for the two loading regimes observed in the rupture kinetics in CACs. Comment: 29 pages, 6 figures, Submitted to J. Chem. Phys |
| Databáze: | OpenAIRE |
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