タンパク質に力を加えると複雑な形が変化する様子を新しいイメージング手法で可視化 New imaging approach visualizes how applying force to proteins alters complex formations
2023-05-04 デューク大学(Duke)
◆生体力学による細胞の構造と振る舞いへの影響を視覚化するための新しいイメージングアプローチであるFTCを使用することにより、他のタンパク質や細胞構造との相互作用を把握することができるようになった。
◆このメカノバイオロジーの研究により、細胞ががん細胞に変異する可能性のある物理的変化を特定することができるようになるため、治療薬の開発に役立つ可能性がある。
<関連情報>
- https://pratt.duke.edu/about/news/proteins-use-force-make-new-connections
- https://www.cell.com/developmental-cell/fulltext/S1534-5807(23)00074-6
フォーカルアドヒージョン内の構成的および文脈特異的な分子張力感受性タンパク質リクルートメントの同定 Identifying constitutive and context-specific molecular-tension-sensitive protein recruitment within focal adhesions
Arnold Tao,Andrew S. LaCroix,T. Curtis Shoyer,Vidya Venkatraman,Karen L. Xu,Bradley Feiger,Brenton D. Hoffman
Developmental Cell Published:March 15, 2023
DOI:https://doi.org/10.1016/j.devcel.2023.02.015
Highlights
•This work develops an approach termed fluorescence-tension co-localization (FTC)
•FTC identifies the recruitment of one protein due to the molecular tension on another
•Vinculin mediates constitutive and context-dependent tension-sensitive recruitment
Summary
Mechanosensitive processes often rely on adhesion structures to strengthen, or mature, in response to applied loads. However, a limited understanding of how the molecular tensions that are experienced by a particular protein affect the recruitment of other proteins represents a major obstacle in the way of deciphering molecular mechanisms that underlie mechanosensitive processes. Here, we describe an imaging-based technique, termed fluorescence-tension co-localization (FTC), for studying molecular-tension-sensitive protein recruitment inside cells. Guided by discrete time Markov chain simulations of protein recruitment, we integrate immunofluorescence labeling, molecular tension sensors, and machine learning to determine the sensitivity, specificity, and context dependence of molecular-tension-sensitive protein recruitment. The application of FTC to the mechanical linker protein vinculin in mouse embryonic fibroblasts reveals constitutive and context-specific molecular-tension-sensitive protein recruitment that varies with adhesion maturation. FTC overcomes limitations associated with the alteration of numerous proteins during the manipulation of cell contractility, providing molecularly specific insights into tension-sensitive protein recruitment.
