The Valentine Lab at the University of California, Santa Barbara
Molecular & Cellular Biomechanics, Biomaterials, Bioadhesion

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  • Motor Protein Motility

    We use advanced microscopy and force spectroscopy techniques to measure the mechanical properties of molecular motor proteins, with a focus on the kinesin-related proteins that participate in axonal transport. Both in vitro and cellular assays are used to investigate kinesin-driven trafficking of cargos. We are particularly interested in how microtubule associated proteins (i.e. EB1, tau) influence kinesin motion and how mulitple kinesin motors cooperate to move cargos in cells.

    Trajectory shows kinesin motion along microtubule (Click to play movie)

    Single Filament Elasticity and Structure

    We measure the flexural rigidity of isolated and fluorescently-labeled filaments by analyzing how their shape fluctuates under thermal excitation. We are particularly interested in how MAPs, nucleotide analogs, and small-molecule stabilizers influence microtubule stiffness.

    Montage of images of microtubules
    (Click to play movie)

    Image of reconstituted cytoskeleton
    Mechanics of the Cytoskeleton

    Cells contain a dynamic and enzymatically active polymer network called the cytoskeleton that allows them to respond to chemical and mechanical inputs in real time. We seek to understand the molecular origins of cytoskeletal strength and shape using novel microscopy and micromanipulation techniques.

    Our results will advance our understanding of important force-sensitive biological processes, inclduing stem cell differentiation and wound healing. More generally, our experiments will provide new insight into the physics of self-assembled systems and will enable the development of novel bio-inspired materials.

    Mussel-inspired wet adhesives

    We investigate the mechanical origins of mussel adhesive strength using natural mussel-derived plaques, as well as synthetic mimics. We use a custom built load frame with dual angle imaging to study the tensile and debonding properties of natural and man-made adhesive structures, and use electron microscopy to study plaque ultrastructure.

    (L) Image of a natural mussel plaque under tensile loading. (R) A PDMS-based synthetic structure with disk + stem geometry.

    Monolayer of human cervical cancer cells
    Force Generation by Living Cells

    Using microscopy and force spectroscopy techniques, we examine the effect of substrate chemistry and mechanics on cell growth and movement. Ultimately, we aim to understand how forces regulate large-scale motion in healthy and diseased tissues, and use that information to develop improved diagnostics and clinical treatments for diseases such as Alzheimer’s and cancer. We are also exploring the effects of confinement and compression in embryonic development.

    Instrument Development

    We are developing a number of novel imaging and force spectroscopy techniques, as well as specialized devices for micro- and nanoscale manipulation of single proteins, filaments, and cells.

    Predictive Modeling of Biological Materials

    We apply traditional engineering tools, including stochastic modeling and finite element analysis, to understand how forces are generated and transmitted in soft biological materials.

    Valentine Laboratory, California NanoSystems Institute, Room 2404, Elings Hall, University of California, Santa Barbara, CA 93106; 805-893-2594.