title: A General Approach for Generating Fluorescent Probes to Visualize Piconewton Forces at the Cell Surface.
abstract: Mechanical forces between cells and their extracellular matrix (ECM) are mediated by dozens of different receptors. These biophysical interactions play fundamental roles in processes ranging from cellular development to tumor progression. However, mapping the spatial and temporal dynamics of tension among various receptor-ligand pairs remains a significant challenge. To address this issue, we have developed a synthetic strategy to generate modular tension probes combining the native chemical ligation (NCL) reaction with solid phase peptide synthesis (SPPS). In principle, this approach accommodates virtually any peptide or expressed protein amenable to NCL. We generated a small library of tension probes displaying different ligands, flexible linkers, and fluorescent reporters, enabling the mapping of integrin and cadherin tension, and demonstrating the first example of long-term (∼3 days) molecular tension imaging. This approach provides a toolset to better understand mechanotransduction events fundamental to cell biology.
authors.affiliation: Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia, United States.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia, United States.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Galior
authors.affiliation: Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia, United States.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia, United States.
authors.forename: Khalid
authors.initials: K
authors.lastname: Salaita
mesh_terms: D000818:Animals; D004285:Dogs; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D016023:Integrins / Q000737:chemistry; D061985:Madin Darby Canine Kidney Cells; D040542:Mechanotransduction, Cellular; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods*; D041681:NIH 3T3 Cells; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000032:analysis / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: D005456:Fluorescent Dyes; D016023:Integrins; D009842:Oligopeptides; D010455:Peptides; D011956:Receptors, Cell Surface; D012235:Rhodamines; D054852:Small Molecule Libraries; D011092:Polyethylene Glycols; C005358:tetramethylrhodamine; C047981:arginyl-glycyl-aspartic acid