Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

18-POS Board 5 MEMBRANE TENSION DRIVES CELL RESPONSE TO POROUS SUBSTRATES: A COMPUTATIONAL STUDY Alyse R Gonthier 1 ; Anna Grosberg 2,3 ; Elliot Botvinick 2 ; Ali Mohraz 1,3 ; 1 University of California, Irvine, Materials Science & Engineering, Irvine, CA, USA 2 University of California, Irvine, Biomedical Engineering, Irvine, CA, USA 3 University of California, Irvine, Chemical & Biomolecular Engineering, Irvine, CA, USA Understanding physical cell-substrate interactions is critical to improving the long-term stability of biomedical implants. Many studies have examined the impact of biochemical cues on immune cell response, but the role of physical and geometrical cues such as local curvature is not as well understood. Recent studies have suggested that local curvatures within a porous material have a significant impact on immune cell behavior, such as macrophage polarization. Specifically, a recently developed porous implant with a unique interconnected and uniform pore structure, called a bijel-templated material or BTM, demonstrated improved vascularization and significantly increased presence of pro-healing macrophages in comparison to the current state- of-the-art. Because of their spontaneous thermodynamic formation process, BTMs have a unique predominance of negative Gaussian curvatures, which can be thought of as saddles, along their internal surfaces. Initial studies suggest that this specific curvature and its impact on membrane tension sensing directly contribute to the increase in pro-healing macrophage presence, and downstream immune benefits. Utilizing a computational modeling approach, this work aims to provide a mechanistic understanding of this special substrate curvature as a direct factor contributing to improved immune response. The model is necessarily developed to emphasize the contribution of membrane tension to overall cell motility and behavior, significantly improving its ability to replicate cell behavior observed in vitro. This combination of computational modeling and in vitro validation predicts a strong, characteristic relationship between unique BTM curvature and cell behavior, in terms of shape and motility. Continuing work will illuminate a mechanistic relationship between this effect of local curvature and the increased pro-healing macrophage population. This would in turn inform improvements to implant success on a broad scale, and significantly contribute to understanding how implantable devices can be optimized for success and longevity in the body without biochemical intervention.

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