DONATE

Staff member

Staff member publications

Zalvidea, D., Castano, O., Baker, S., Castro, N., Engel, E., Trepat, X., (2019). Time-lapse intravital imaging of biomaterials integration in tissues using a multicolor multiphoton microscope Novel lasers, instruments and technology 2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference , IEEE (Munich, Germany) OSA Technical Digest (Optical Society of America, 2019), paper cl_3_1

Different mechanisms are triggered when tissue is exposed to a biomaterial. The success of the biomaterial targeted process, like the release of chemicals, promoted angiogenesis, tissue regeneration, etc. depends on its integration in the tissue [1]. Studying this interaction in vivo requires the ability to image simultaneously deep immersed proteins and biomaterials with high resolution and low damage. Several methods offer solutions but only multiphoton microscopy (MM) has the ability to image with high resolution deep inside the sample. Why is not MM more extensively applied as a platform for investigating biomaterial integration in vivo? The high cost of the typical source for multiphoton microscopy is a clear limitation. Furthermore, imaging several channels simultaneously becomes out of reach for most of the labs.

JTD


Elosegui, Alberto, Oria, Roger, Chen, Yunfeng, Kosmalska, Anita, Perez-Gonzalez, Carlos, Castro, Natalia, Zhu, Cheng, Trepat, Xavier, Roca-Cusachs, Pere, (2016). Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity Nature Cell Biology 18, (5), 540-548

Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response.

JTD