Program in Chemical Biology. Dev. et al. High-resolution microtubule structures reveal the structural transitions in αβ-tubulin upon GTP hydrolysis. Without it, the fragile fundamental unit of life would crumble. For instance, the intrinsic dynamics of microtubules drive cell division by separating duplicate sets of genetic material, while those of actin filaments power cellular movement. Taken together, Alushin’s studies support a broader goal: to understand the means by which mechanical forces influence both a cell’s characteristics and its behavior. To learn more about their areas of expertise, use the focus area filters below to view faculty profiles in your area of interest. “But before our study, there was no research proving that stretching actin conveys a mechanical signal to proteins that can sense this mechanical force.”, A “floppy tail” receives the transmission. All rights reserved. April 06, 2020. Both types of filaments additionally interact with hundreds of binding partners and serve as tracks for molecular motor proteins, providing the infrastructure for organizing and shaping the cell. Short-term exposure to mechanical force can prompt cells to migrate, or, in the case of cancer, metastasize. “By precisely defining the force-detector in α-catenin, we will enable researchers to figure out exactly what its function is in mechanical signaling.”, “We suspect that there are hundreds of other proteins that directly sense force transmitted by actin,” adds Mei. Over the long term, his group seeks to understand how changes to actin are linked to alterations in gene expression in development and disease. Now scientists are ready to explore the mechanics of being alive. The structural basis of actin organization by vinculin and metavinculin. To investigate these interactions, Alushin employs cryo-electron microscopy along with biochemical and biophysical approaches. The largest map of gene expression in over 4 million human cells charts the dynamic path to forming different organs. “Our work provides the foundation and the molecular details to begin searching for all of the other force-sensitive proteins.”, Gregory M. Alushin Program, and the Tri-Institutional Ph.D. Studies how cells sense and respond to mechanical forces. B.A. Cryo-electron microscopy reconstructions of the cell adhesion proteins vinculin (left, orange) and a-catenin (right, pink) bound to actin filaments (blue). Alushin is using cryo-electron microscopy to further define the interactions between actin and its many binding partners in order to better understand the context in which these sensors work. But physical forces also pass crucial signals onto cells through an entirely different phenomenon in which molecules push and pull on each other, perpetually coming together and dissociating, Meet the scientific leaders who are changing medicine, Peek inside our 70 biomedical laboratories, Learn more about our flexible, supportive academic programs, Learn about the breakthroughs happening every day, Hear from the world’s leading speakers and thinkers, We’ve spent 119 years perfecting the bioscience institute, Conservation of resources is hardwired into the genetic code, New atlas reveals the journey of human cells throughout development, Laboratory of Structural Biophysics and Mechanobiology, Molecular mechanism for direct actin force-sensing by α-catenin. With the help of advanced electron microscopy techniques, the researchers homed in on the crucial difference between α-catenin and vinculin. He and his co-workers suspected that actin was relaying a perfectly good mechanical signal, but that only the floppy tail of α-catenin was prepared to receive it. The Ndc80 kinetochore complex forms oligomeric arrays along microtubules. Biol. 1969 (physics) Professional Experience. While decades of research have shed light on the chemical signaling process, the particulars of mechanical signaling are still poorly understood. Working with Rodrigues, Shyer will continue to fuse mechanical and molecular tactics to better understand pattern formation and tissue development. But it remained unclear how cells pass a mechanical signal from their environment along to actin, and how actin then relays that signal to either beckon adhesion proteins or push them away. Mechanical and Civil Engineers shape our physical environment from the cities we live in, the machines we use, the way we travel, the energy that powers these to delivering the water we need. : 514-398-3068 email Nonlinear vibrations and stability of shells with and without fluid-structure interaction. In a painstaking experiment, scientists suspended a single protein filament between two microscopic beads. Alushin’s lab now focuses on actin’s contribution to cellular mechanosensation. The Rockefeller University, Ph.D. 1974 (theoretical physics) Reed College, 1965-69, B.A. J. Mol. Alushin’s long-term goal is to explore this link between sustained mechanical forces and gene expression. Assistant Professor A good deal of actin’s activity is based on mechanical signaling; it appears to somehow sense physical feedback from the environment and respond accordingly. Alushin studies how these filaments, themselves macromolecular assemblies composed of repeating protein subunits arranged like steps in a spiral staircase, physically interface with collaborating proteins. Cell 157, 1117–1129 (2014). “The idea that actin filaments could potentially be tiny stretchy tension sensors in the cell has been banging around in the literature for a while, but I think we really proved it here,” says Gregory M. Alushin, assistant professor and head of the Laboratory of Structural Biophysics and Mechanobiology. Ti, S.C. et al. sadera@umich.edu. Microtubules and actin are two of the predominant classes of filaments, and each has distinct roles. Cells are supported by a cytoskeleton made of protein filaments that provide it with an internal structure and facilitate movement. Today, renamed The Rockefeller University, it is one of the foremost research centers in the world, with a world-class faculty. They observed that actin bound α-catenin better while they were pulling on it, implying that actin was transmitting a mechanical signal to α-catenin, and that α-catenin had the capacity to receive this signal. Alushin notes that, while α-catenin and its floppy tail may eventually become an appealing target for clinical therapies, the new findings are first and foremost a coup for the burgeoning field of mechanobiology, which studies how mechanical forces drive crucial processes at the cellular level. Kim, L.Y. Departments and services at The Rockefeller University support our mission of science for the benefit of humanity by ensuring that researchers have the support and resources necessary to carry out their groundbreaking work. It is clear, for instance, that when a cell clings to the bottom of a petri dish or makes contact with neighboring cells, its interaction with its surroundings is driven by actin, which binds to so-called adhesion proteins in the cell’s outer rim. Rockefeller’s culture is built on genuine dedication to promoting scientific discovery. By literally stretching individual actin filaments, the researchers determined a process by which actin transmits cellular mechanical messages to other proteins.