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Title:Structural Basis of the Tensile Strength of Protein Complexes Mediating Cell Adhesion
Author(s):Bayas, Marco Vinicio
Doctoral Committee Chair(s):Deborah Leckband
Department / Program:Biophysics and Computational Biology
Discipline:Biophysics and Computational Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Physics, Molecular
Abstract:This study explores the behaviour of adhesive complexes of cell adhesion molecules undergoing forced detachment. Molecular-forces measurements combined with Steered Molecular Dynamic (SMD) simulations were used to investigate the mechanical response of the CD2 C58 and hemophilic C-cadherin bonds. The CD2-CD58 adhesive complex, important for the adaptive immune response, contains several salt-bridges in the adhesive interface. SMD simulations showed that these inter-protein salt bridges contribute independently to the tensile strength of the complex. Consistent with this, force measurements with the Surface Force Apparatus (SFA) demonstrated that the elimination of single salt bridges weakens the bond. The corresponding loss in adhesion energy of the CD2-CD58 complex correlates with the importance of the salt bridges observed in the simulations. These findings correlate closely with the effect of the elimination of single salt bridges observed in cell aggregation assays and binding measurements. On the other hand, the hemophilic C-cadherin interaction determines specific cell-cell adhesion during development in Xenopus laevis . Single molecule force spectroscopy was used to characterize the multiple bound states between C-cadherin ectodomains. The experiments showed two short-lived bound states associated with the two outermost ectodomains and two long-lived states associated with the full ectodomain. It is likely that the two short-lived states are involved in the specificity of the interaction since previous studies showed that the corresponding states in E-cadherin have different lifetimes. In addition, SMD simulations of the forced dissociation of the strand dieter of C-cadherin suggested a mechanism for the specificity of cadherin interactions.
Issue Date:2005
Type:Text
Language:English
Description:179 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005.
URI:http://hdl.handle.net/2142/85446
Other Identifier(s):(MiAaPQ)AAI3198923
Date Available in IDEALS:2015-09-25
Date Deposited:2005


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