Biomechanical Regulation in Human Cells
Paul R. Standley, Ph.D.
University of Arizona College of Medicine - Phoenix

Cell culture has been extensively utilized for decades to model numerous biological systems in vitro. While scientists have successfully reproduced many of the requirements of the in vivo environment within these cultures, mimicking one key variable has lags behind the others: that being biomechanical cues.

Two major foci of my laboratory are:

mimicking arterial pressure waveforms in vascular smooth muscle cultures in order to investigate autocrine mediators of cell growth and inflammation thought to be complicit in diseases such as hypertension and atherosclerosis, and

mimicking manual medicine waveforms in human fibroblast cultures in order to build a cell/molecular evidence base to explain clinical efficacy of manual treatments used by osteopaths, chiropractors, physical therapists and others.

Common findings in both studies include the observations that biomechanical strain:

alters cell phenotype

directs cell migration,

modulates cell proliferation, and

mediates growth factor and inflammatory cytokine expression responsible for phenotypic, migratory and proliferative modulation.
Our most recent data suggests that in addition to strain frequency, magnitude and duration, strain direction uniquely regulates these cell characteristics. For example, human fibroblasts strained equiradially vs. heterobiaxially (all other strain variables equal) display divergent cell morphology, proliferative indices, and cytokine expression profiles. These data suggest that manual medicine treatments may be exploited best by realizing the intricacies of biomechanical strain variables that define such treatments.

In summary, biomechanical strain regulation of growth factor and cytokine expression in human cells may speak to the physiological basis for many diseases including cardiovascular disease and somatic dysfunction. The search for the mechanosensors responsible for gene regulation is an important one, and one that will undoubtedly lead to optimization of current and development of future treatment modalities.

MetroCon 2007

“Innovating for Society”

Biotechnologies

Dr. Standley trained as a vascular physiologist at Wayne State University School of Medicine in Detroit, Michigan. His first faculty appointments were in the Departments of Physiology and Internal Medicine where he continued his work investigating the vascular effects of insulin and its actions as a calcium channel blocking agent. Upon his move to Arizona in 1996 to help found the Arizona College of Osteopathic Medicine at Midwestern University, his research gained new focus in the field of biophysical regulation of gene expression in vascular smooth muscle. During his tenure at MWU, he also developed a new innovative medical physiology curriculum there and has taught medical students in all subdisciplines of medical physiology for 12 years. Dr. Standley moved to the University of Arizona College of Medicine – Phoenix in 2006 to help found its new medical school track. Here, he serves as the block director for the cardiovascular/pulmonary/renal section of the year I medical curriculum. In addition, he continues his NIH-funded research program, continuing to investigate how biophysical stimuli regulate cytokine and growth gene expression in vascular smooth muscle and fascial fibroblasts. His academic passions include student-centric instruction / curriculum development, his ongoing cellular biomechanics research and taking modern medical information into the community using a variety of outreach strategies.

Ph.D. Physiology (1992) Wayne State University School of Medicine – Detroit, MI

Post-Doc, Vascular Endocrinology and Hypertension; Wayne State University Department of Internal Medicine

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