EAGER: Individual and Collective Cellular Osteoclast Behavior in Bone Dynamics

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

In vertebrates, bones serve multiple functions, including organ protection, structural support during locomotion, and mineral homeostasis. Bones are not static structures but are dynamic multiscale tissues, comprised of cells, organic material, and inorganic molecules at the micro-level, transitioning to cortical and cancellous bone at the macro-level. This system continuously responds to local molecular and cellular milieu, physical stress and strain, and distant hormonal influences. Three main cell types dominate the cellular mechanisms governing bone microscale response: osteoblasts (create bone), osteocytes (maintain bone), and osteoclasts (degrade bone). While the gene expression and cellular mechanisms governing bone tissue are well-understood, fundamental principles of dynamic remodeling are only recently being investigated. Hence, the emergence of bone properties from lower-level processes remains an open question. This is particularly intriguing as the collective functions without any cell having knowledge of the global state. In this award, a physician specializing in orthopedic clinical research focusing on bone biology, fracture repair, and arthrodesis healing, and a physicist specializing in individual and collective organism and robot dynamic, will study osteoclasts, multinucleated giant cells. Osteoclasts play a critical role in bone resorption, preparing the system for remodeling. These cells crawl along surfaces, chemically eroding material, and leave tracks that are subsequently filled in by osteoblasts. While knowledge exists about osteoclast development and function, limited research has been conducted to comprehend the physics of osteoclast motility, bone degradation patterns, and how cell heterogeneity and morphology change in response to environmental stimuli and/or affect function. Further, the interactions among these cell collectives remain poorly elucidated. To advance understanding of bone resorption, the investigators will observe the movement of individual and collectives of multinucleated osteoclast cells in controlled laboratory experiments, mimicking bone tissue and various material surfaces. Scientifically, individual and collective dynamics hold significance for researchers in various fields, from active soft matter physics to computer scientists focusing on collective decision-making. Practically, this work forms the basis for deeply understanding bone tissue function and responses to environmental stimuli, offering potential for new translational treatment targets. Osteoporotic fractures, rising with age, contribute to an estimated healthcare cost exceeding 5 trillion dollars annually in the US and Canada. The investigators will connect Orthopedic Surgeons and physicists, fostering exploration and collaboration through invitations to the APS March Meeting, the annual iPoLS SRN meeting, and the Orthopaedic Research Society annual meeting. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.