TY - JOUR
T1 - Theory and simulations of adhesion receptor dimerization on membrane surfaces
AU - Wu, Yinghao
AU - Honig, Barry
AU - Ben-Shaul, Avinoam
N1 - Funding Information:
The financial support of the US-Israel Binational Science Foundation (grant No. 659/06 to A.B.-S. and B.H.), and the U.S. National Science Foundation (grant No. MCB 0918535 to B.H.) is gratefully acknowledged. A.B.-S. also thanks the Israel Science Foundation (grant No. 1448/10) and the Archie and Marjorie Sherman chair.
PY - 2013
Y1 - 2013
N2 - The equilibrium constants of trans and cis dimerization of membrane bound (2D) and freely moving (3D) adhesion receptors are expressed and compared using elementary statistical-thermodynamics. Both processes are mediated by the binding of extracellular subdomains whose range of motion in the 2D environment is reduced upon dimerization, defining a thin reaction shell where dimer formation and dissociation take place. We show that the ratio between the 2D and 3D equilibrium constants can be expressed as a product of individual factors describing, respectively, the spatial ranges of motions of the adhesive domains, and their rotational freedom within the reaction shell. The results predicted by the theory are compared to those obtained from a novel, to our knowledge, dynamical simulations methodology, whereby pairs of receptors perform realistic translational, internal, and rotational motions in 2D and 3D. We use cadherins as our model system. The theory and simulations explain how the strength of cis and trans interactions of adhesive receptors are affected both by their presence in the constrained intermembrane space and by the 2D environment of membrane surfaces. Our work provides fundamental insights as to the mechanism of lateral clustering of adhesion receptors after cell-cell contact and, more generally, to the formation of lateral microclusters of proteins on cell surfaces.
AB - The equilibrium constants of trans and cis dimerization of membrane bound (2D) and freely moving (3D) adhesion receptors are expressed and compared using elementary statistical-thermodynamics. Both processes are mediated by the binding of extracellular subdomains whose range of motion in the 2D environment is reduced upon dimerization, defining a thin reaction shell where dimer formation and dissociation take place. We show that the ratio between the 2D and 3D equilibrium constants can be expressed as a product of individual factors describing, respectively, the spatial ranges of motions of the adhesive domains, and their rotational freedom within the reaction shell. The results predicted by the theory are compared to those obtained from a novel, to our knowledge, dynamical simulations methodology, whereby pairs of receptors perform realistic translational, internal, and rotational motions in 2D and 3D. We use cadherins as our model system. The theory and simulations explain how the strength of cis and trans interactions of adhesive receptors are affected both by their presence in the constrained intermembrane space and by the 2D environment of membrane surfaces. Our work provides fundamental insights as to the mechanism of lateral clustering of adhesion receptors after cell-cell contact and, more generally, to the formation of lateral microclusters of proteins on cell surfaces.
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U2 - 10.1016/j.bpj.2013.02.009
DO - 10.1016/j.bpj.2013.02.009
M3 - Article
C2 - 23528081
AN - SCOPUS:84877071090
SN - 0006-3495
VL - 104
SP - 1221
EP - 1229
JO - Biophysical journal
JF - Biophysical journal
IS - 6
ER -