Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

50-POS Board 17 TENSION-BASED REGULATION OF FOCAL ADHESIONS AND CLATHRIN CONTAINING ADHESION COMPLEXES IN CANCER PROGRESSION

Umidahan Djakbarova 1 ; Yasaman Madraki 2 ; Ata Akatay 3 ; Emily Chan 1 ; Comert Kural 1 ; 1 The Ohio State University, Physics, Columbus, OH, USA

2 Roche, Boston, MA, USA 3 TUBITAK, Istanbul, Turkey

Integrin-based adhesion complexes play critical roles in a multitude of cellular processes, such as cellular proliferation, differentiation, and motility. Despite extensive research on the canonical focal adhesion complexes (FAs), the regulation, coordination, and physiological roles of newly identified clathrin-containing adhesion complexes (CCACs) remain unclear. In this study, we elucidated the spatiotemporal regulation of FAs and CCACs by plasma membrane tension and actomyosin contractility in a breast cancer model. By using single-molecule force spectroscopy coupled with live-cell fluorescent microscopy, we found that FAs and CCACs are mutually exclusive and inversely regulated by the modulation of plasma membrane tension. Our results show that high membrane tension is associated with cortical actin networks and high density of CCACs. In contrast, low membrane tension facilitates stress fiber formation, thereby increasing actomyosin contractility and the formation of FAs. We also found that the stability of FAs and CCACs is governed by their mutual competition for binding to integrin αVβ5 adhesion sites and this competitive interaction is modulated by the level of membrane tension. Specifically, high membrane tension favors CCAC localization to αVβ5 sites , while low membrane tension triggers dissociation of CCACs, thereby allowing localization of FAs. In addition, we observed that low membrane tension promotes cell cycle progression, spreading, and migration by upregulating FA dynamics. Whereas high membrane tension, which increases CCAC density, acts as a tumor suppressor by arresting cells at the G1 phase of the cell cycle and reducing their spreading and motility. Overall, our study provides new insights into the reciprocal regulation of adhesion modes in cancer progression and highlights the potential of manipulating membrane tension as a potent target for therapeutic interventions.

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