CAREER: Remodeling and Damage of the Tendon Attachment During Postnatal Growth

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This Faculty Early Career Development (CAREER) grant will control the remodeling of tendon and its attachment to bone during growth. Postnatal growth places unique mechanical stresses on bones and muscles. As skeletal muscles get stronger and motor skills improve, the flexibility of connective tissues like tendons and attachments decreases. Tendons and their attachments transmit muscle loads to bone, so changes in their flexibility affect bone loading and movement. Muscle unloading occurs during postnatal growth. This unloading has detrimental effects on the structure and function of the tendon attachment. However, the effect that muscle overloading has on the growing skeleton remains unknown. This is because the ability to control skeletal muscle activation during periods of rapid growth and development is challenging. Optogenetics has emerged as a powerful technique for spatial and temporal control of cells, including muscle cells. The research group will use optogenetic techniques to control muscle contraction by the exposure of blue light through skin. This will allow them to precisely increase mechanical loading at the tendon attachment during the early stages of postnatal growth. They will then evaluate the effect of increased muscle loading on the tendons and their attachment. Specifically, they will measure outcomes of remodeling and damage during growth and aging. Findings from this work will inform rehabilitative strategies to maintain musculoskeletal health across the lifespan. This award will also support a partnership between the investigators and the regional teachers for the presentation of seminars on the Science of Movement and development of K-12 curriculum units by local area teachers. The investigators will work with K12 teachers to implement, assess, and publish curriculum units. Furthermore, the investigators will improve their own university teaching by learning from the K12 teachers.In this CAREER project, the PI will use an in vivo optogenetic platform to measure structural, mechanical, and molecular changes induced by remodeling and damage of the tendon attachment that are driven by frequency-, magnitude-, and duration-dependent changes in muscle loading, both during postnatal growth (Objective 1) and in the mature and aging attachment (Objective 2). This work is transformative in nature because the experiments merge together cross-disciplinary approaches using innovative techniques from neuroscience (optogenetics), chemistry (collagen like peptides), life sciences (laser capture microdissection), biomechanics (in vivo isometric joint torque), and the investigator’s expertise (mechanobiology of the tendon attachment). This program will evaluate the effect of inducible muscle loading on measurable outcomes of remodeling and damage of tendon attachments during growth and aging. Findings from this CAREER will fill a knowledge gap in our basic understanding of attachment mechanobiology across the lifespan and reveal biomechanical adaptations associated with mechanically-induced remodeling and damage. The investigator will engage with local K12 educators and continue to mentor PhD, undergraduate, and high school students in engineering research focused on the mechanisms of tissue remodeling during growth and aging.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.