title: Elasticity of the Transition State Leading to an Unexpected Mechanical Stabilization of Titin Immunoglobulin Domains.
abstract: The giant protein titin plays a critical role in regulating the passive elasticity of muscles, mainly through the stochastic unfolding and refolding of its numerous immunoglobulin domains in the I-band of sarcomeres. The unfolding dynamics of titin immunoglobulin domains at a force range greater than 100 pN has been studied by atomic force microscopy, while that at smaller physiological forces has not been measured before. By using magnetic tweezers, it is found that the titin I27 domain unfolds in a surprising non-monotonic force-dependent manner at forces smaller than 100 pN, with the slowest unfolding rate occurring around 22 pN. We further demonstrate that a model with single unfolding pathway taking into account the elasticity of the transition state can reproduce the experimental results. These results provide important novel insights into the regulation mechanism of the passive elasticity of muscle tissues.
authors.affiliation: Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Lab for Soft Functional Materials Research, Department of Physics, Xiamen University, Xiamen, Fujian, 361005, China.|Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore.|Department of Physics, National University of Singapore, Singapore, 117542, Singapore.|Centre for Bioimaging Sciences, National University of Singapore, Singapore, 117546, Singapore.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore.|Department of Physics, National University of Singapore, Singapore, 117542, Singapore.|Centre for Bioimaging Sciences, National University of Singapore, Singapore, 117546, Singapore.
authors.forename: Shimin
authors.initials: S
authors.lastname: Le
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore.|Department of Physics, National University of Singapore, Singapore, 117542, Singapore.|Centre for Bioimaging Sciences, National University of Singapore, Singapore, 117546, Singapore.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Yao
authors.affiliation: Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Lab for Soft Functional Materials Research, Department of Physics, Xiamen University, Xiamen, Fujian, 361005, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qian
authors.affiliation: College of Physics, University of Chinese Academy of Sciences, Beijing, 100190, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore.|Department of Physics, National University of Singapore, Singapore, 117542, Singapore.|Centre for Bioimaging Sciences, National University of Singapore, Singapore, 117546, Singapore.
authors.forename: Jie
authors.identifier: 0000-0002-8555-7291
authors.initials: J
authors.lastname: Yan
authors.affiliation: Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Lab for Soft Functional Materials Research, Department of Physics, Xiamen University, Xiamen, Fujian, 361005, China.
authors.forename: Hu
authors.identifier: 0000-0002-5958-9361
authors.initials: H
authors.lastname: Chen
mesh_terms: D064211:Connectin / Q000737:chemistry* / Q000276:immunology*; D004548:Elasticity; D006801:Humans; D000070557:Immunoglobulin Domains / Q000276:immunology*; D055550:Protein Stability
chemical_list: D064211:Connectin; C577285:TTN protein, human
keywords: Bell's model; catch bonds; protein unfolding; titin; transition states