Title: Mechanophysiology of organs for disease classification and diagnosisAuthor: Neelesh A. PatankarAddress: Department of Mechanical Engineering, and Engineering Sciences & Applied Math, Northwestern University

Mechanophysiology is the study of the mechanics of the functioning (physiology) of organs. Our ultimate goal is to translate mechanophysiology into clinical practice. Our focus is on organs where mechanics is the key determinant of its function. We hypothesize that it should be possible to classify normal and disease groups for such organs in a mechanical parameter space. This is the virtual disease landscape (VDL), which we have demonstrated successfully for esophageal pathologies. In principle the mechanical parameter space could be also organized in terms of non-dimensional numbers, which would define “disease basis vectors.” This parameter space helps define the “mechanical health” of the organ and systematically develop new diagnostic metrics called physiomarkers. Our eventual goal is to correlate VDL to transcriptomics data and develop a transcription/gene to function mapping for organs. Overall, the mechanophysiology framework is anchored on a portfolio of mechanics-informed imaging toolkits, virtual disease landscapes in mechanical parameter spaces, mechanics-based physiomarkers, and mechanistic underpinnings of pathologies. Using this framework, we are interrogating esophagus, aorta, lung, urinary tract, and uterus physiologies. As examples, foundational questions pertaining few pathologies will be presented, including: 1. Can mechanical signatures be identified and used in diagnosing eosinophilic esophagitis (a disease identified only since early ‘90s but now one of the major causes of digestive system dysfunction)? 2. Can emergent solutions of neuromechanical dynamics explain some of the motility disorders of the esophagus? 3. Is it possible to predict the onset of aortic aneurysm (“the silent killer” that took the life of Grant Wahl – an American soccer sportswriter – during 2022 FIFA world cup)? The current standard of care has no predictive capability - aneurysms only get diagnosed, if at all, after the fact.