Speaker: Dr. Richard Superfine, UNC-CH

Speaker: Dr. Richard Superfine, Associate Professor, Department Chair UNC-Chapel Hill Department of Applied Physical Sciences

Title: Combining Volumetric Morphodynamics and Force Measurements for Understanding Cell Mechanobiology in Space and Time

Abstract:  The mechanical component of biology, from single molecules to cells to tissues, has been demonstrated to control the identity, movement, and fate of cells, and is relevant in diseases from cancer to immunology to muscular dystrophy. Understanding the origins and responses of cellular forces requires the resolving of the spatiotemporal structure of cellular components and biochemical activity, time-correlated with cellular forces. To accomplish this, we have combined volumetric light-sheet imaging with atomic force microscopy to obtain multicolor, 3D movies of cellular structure correlated with AFM characterized forces. Our light-sheet microscopy is capable of real-time imaging in the vertical X-Z plane at 100FPS, time-correlated with AFM forces, as well as volumetric imaging at ~ 1 cell volume per second. By designing our instrumentation to perform all image tuning and scanning while leaving the specimen and objective completely fixed with respect to the lab frame (and hence the AFM tip), we can maintain single-molecule force resolution while performing our imaging. We have applied this system to understand the complex biological phenomena of phagocytosis and nuclear mechanics. Phagocytosis is the remarkable coordinated process by which a macrophage can engulf large particles and cells. We engage a beaded AFM cantilever against a macrophage and collect volumetric images of the actin cytoskeleton during phagocytosis to image filipodia dynamics and phagocytic cup formation in real-time, and correlate surface and internal actin dynamics with engulfment forces. The role of the nuclear envelope and nuclear contents in nuclear mechanical properties, and the consequences of nuclear compression in gene expression and DNA damage, are all of great interest. We perform volumetric imaging of cell nuclei under AFM compression while imaging the nuclear envelope and chromatin to assign mechanical properties to specific components, while also imaging DNA damage induced by the AFM compressions.

Biography: Richard Superfine, Taylor-Williams Distinguished Professor and Chair of Applied Physical Sciences at the University of North Carolina at Chapel Hill received his B.S. in engineering physics from Lehigh University and worked at AT&T Bell Laboratories for three years before moving to the University of California, Berkeley to obtain his Physics Ph.D. in laser studies of molecular surfaces. Since arriving at UNC-Chapel Hill, his research includes the study of nanoscale phenomena in nanodevices, biological forces, and the systems biology of lung defense. His group has led major grants in instrumentation develop the principal investigator of the UNC NIH center for Computer Integrated Systems for Manipulation and Microscopy (CISMM.org) which develops tools for biomedical sciences. He has led major research funding of over $40 million in grants including multi-investigator, interdisciplinary projects studying mucociliary clearance in the lung and the application of visualization and modeling for treatments of upper airway breathing disorders, and instrumentation development for force measurements in biological systems. To broaden the impact of his group’s work, one microscopy system, the nanoManipulator, has been commercialized and has won an R&D 100 award (2001). Most recently, he is co-founder and board chair of Redbud Labs, a startup company developing chip-based diagnostic technologies. In his administrative roles at UNC, Superfine has led the development of the UNC makerspace network called BeAM (Be A Maker), which currently constitutes over 5,000 sq ft of makerspaces. Open to all students, staff, and faculty throughout UNC, BeAM has trained over 5,000 new users, matching the demographics of the university, and engaged students in over 170 courses. Superfine now chairs the Department of Applied Physical Sciences (APS), the first new science department at UNC in over 40 years. The goal of APS is to broaden the impact of the UNC through a convergent engineering approach that bridges discovery science to solutions in the world.