Open AccessLabel-free Single-Molecule Quantification of Rapamycin-induced FKBP–FRB Dimerization for Direct Control of Cellular Mechanotransduction
Author(s) -
Yinan Wang,
Samuel F. H. Barnett,
Shimin Le,
Zhenhuan Guo,
Xueying Zhong,
Pakorn Kanchanawong,
Jie Yan
Publication year - 2019
Publication title -
nano letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.853
H-Index - 488
eISSN - 1530-6992
pISSN - 1530-6984
DOI - 10.1021/acs.nanolett.9b03364
Subject(s) - fkbp , mechanotransduction , ternary complex , chemistry , biophysics , ternary operation , nanotechnology , microbiology and biotechnology , materials science , biochemistry , biology , computer science , programming language , enzyme
Chemically induced dimerization (CID) has been applied to study numerous biological processes and has important pharmacological applications. However, the complex multistep interactions under various physical constraints involved in CID impose a great challenge for the quantification of the interactions. Furthermore, the mechanical stability of the ternary complexes has not been characterized; hence, their potential application in mechanotransduction studies remains unclear. Here, we report a single-molecule detector that can accurately quantify almost all key interactions involved in CID and the mechanical stability of the ternary complex, in a label-free manner. Its application is demonstrated using rapamycin-induced heterodimerization of FRB and FKBP as an example. We revealed the sufficient mechanical stability of the FKBP/rapamycin/FRB ternary complex and demonstrated its utility in the precise switching of talin-mediated force transmission in integrin-based cell adhesions.