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There’s a time and a place: Biological discovery with spatially and temporally engineered materials

Banff International Research Station for Mathematical Innovation and Discovery

A key goal within the mechanobiology field over the past 25 years has been to understand how biophysical properties of the microenvironment control cellular mechanics and phenotype. Historically, the vast majority of discovery in this area has relied on static and spatially uniform extracellular matrix platforms. While such approaches have been enormously powerful, they are often poorly suited to probing the dynamic mechanical interplay between a cell and its microenvironment. At the same time, these platforms paradoxically create large heterogeneities in cell size, shape, and cytoarchitecture that can make it challenging to quantify regulatory relationships. In this presentation I will discuss recent efforts my colleagues and I have made to exploit next-generation matrix platforms whose material properties may be controlled in both time and space. First, I will discuss our use of a polymer hydrogel system that may be reversibly stiffened and softened through the use of oligonucleotide-based crosslinks, which we have used to identify a critical time window for mechanosensitive neural stem cell lineage commitment. This system has also led us to discover an unexpected and non-canonical role for the transcriptional co-activator YAP in determining cell fate. Second, I will describe our combined use of single-cell photopatterning and femtosecond laser nanosurgery to probe the viscoelastic properties of actomyosin stress fibers with tightly standardized positions and lengths. This approach has allowed us to elucidate relationships between fiber elastic energy and length with unprecedented clarity, as well as gain new insight into how tension within a single fiber is governed by the properties of the surrounding cytoskeletal network. The models we develop in these stereotyped settings allow us to explain propagation of tension in more physiological settings, including the coupling of cytoskeletal tension across cells within a monolayer. An important challenge for the next 25 years of mechanobiology will be to refine and exploit these engineered platforms for mechanistic discovery and technology development.

Mathematics; Mechanics of deformable solids; Biology and other natural sciences; Mathematical biology

video/mp4

Author affiliation: University of California, Berkeley

2017-06-21

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/62048

Unreviewed

http://creativecommons.org/licenses/by-nc-nd/4.0/