Cellular Mechanophenotype Effects on Multicellular Organization and Differentiation

Date(s) - 09/25/2017
3:00 pm

Eric M. Darling, Ph.D., Associate Professor of Medical Science, Engineering, and Orthopaedics, Department of Molecular Pharmacology, Physiology, and Biotechnology, Center for Biomedical Engineering, Brown University


Elastic and viscoelastic properties can be used to describe whole-cell mechanophenotype, which has emerged as a viable biomarker and descriptor of cell function and fate. The work presented in this seminar will focus on how inherent cellular stiffness can influence organization in both 2D and 3D systems. This will be demonstrated through three recent studies from the Darling Lab. In the first, mechanically distinct cell lines were engineered to allow for a well-defined investigation of cell-cell-substrate interactions. Stiff and soft cell lines derived from a common background strain were grown on compliant substrates with elasticities above, matching, or below the average elasticity of a given cell line. Multicellular organization varied across the different combinations, suggesting an assembly phenomenon that depends on both the mechanical properties of substrate and cells. In the latter two studies, cell mimicking microparticles (CMMPs) were fabricated to reproduce the size and stiffness of living cells. These were then combined with adipose-derived stem cells to determine their influence on microtissue self-assembly. Results showed that cells only interacted with ligand-coated CMMPs, and within hours to days, a self-sorting process could be observed. The biochemical and mechanical characteristics of differentiating microtissues were also investigated to determine whether CMMPs could serve as either a scaffold material or mechanical dopant.

Brief bio:

Eric M. Darling is an Associate Professor of Medical Science, Orthopaedics, and Engineering in the Department of Molecular Pharmacology, Physiology, & Biotechnology at Brown University. He also is an active investigator and trainer in the Center for Biomedical Engineering. He received a B.S. in engineering from Harvey Mudd College, a Ph.D. in bioengineering from Rice University, and post-doctoral training in orthopaedic research at Duke University. His research involves mechanobiology, mesenchymal stem cells, and musculoskeletal tissue regeneration, with a primary focus on understanding cellular heterogeneity and its effects on both fundamental phenomena and translational applications. Central to this pursuit has been the identification of novel biological and mechanical markers for enriching high-value cell populations. Recent work in his group has focused on two, novel cellular characteristics: single-cell mechanophenotype and live-cell gene expression.

Dr. Darling’s research has been continuously funded by NIH/NSF since 2004. He received a Ruth L. Kirschstein National Research Service Award (NIH, F32) as a post-doctoral fellow, a Pathway to Independence Award (NIH, K99/R00) as a young investigator, and more recently NSF CAREER and EAGER Awards and an NIH R01 for projects investigating mesenchymal stem cell heterogeneity. He has authored numerous scientific articles, a textbook on articular cartilage, and is an Associate Editor for the Annals of Biomedical Engineering. Dr. Darling has also served as the director of Brown University’s Biomedical Engineering Graduate Program since 2010.