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Brian P. Helmke

Brian P. Helmke

Primary Appointment

  • Associate Professor, Biomedical Engineering

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Research Interest(s)

Intracellular Mechanics and Cell Function

Research Description

Living cells and tissues adapt to their environment by altering structure, gene and protein expression, and biochemical functions. For example, endothelial cells lining the artery wall at the blood tissue interface experience fluid mechanical forces that vary with time and location along the artery. However, the mechanisms by which cells transduce mechanical stimuli into biochemical signals are not well understood. Our laboratory employs a multidisciplinary biomedical engineering approach to understand the relationship between intracellular mechanics and cell function.

Several tools are used for investigating cellular mechanotransduction. Expression of green fluorescent protein (GFP) fused to cytoskeletal or other proteins makes it possible to visualize endogenous intracellular structures, and fluorescence probes enable detection of intracellular signaling molecules such as nitric oxide. High-resolution optical sectioning microscopy, deconvolution, and 3-D image restoration provide quantitative spatial and temporal information. Quantitative image analysis tools analyze intracellular movement, molecular interactions, and biochemical response. Nanotechnology-based structures control mechanical stimuli at the length scale of individual protein structures near the cell surface. Engineering nanoscale spatial cues into the cell’s local environment will enable rational design of cell phenotype for regenerative medicine and tissue engineering. Thus, projects in our laboratory bring together a joint biomedical engineering, materials science, and molecular biology approach to understanding cellular physiology.

Selected Publications

  • Sinha S, Wamhoff B, Hoofnagle M, Thomas J, Neppl R, Deering T, Helmke B, Bowles D, Somlyo A, Owens G. Assessment of contractility of purified smooth muscle cells derived from embryonic stem cells. Stem cells (Dayton, Ohio). 2006;24(7): 1678-88. PMID: 16601077
  • Orr A, Helmke B, Blackman B, Schwartz M. Mechanisms of mechanotransduction. Developmental cell. 2006;10(1): 11-20. PMID: 16399074
  • Helmke B, Minerick A. Designing a nano-interface in a microfluidic chip to probe living cells: challenges and perspectives. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(17): 6419-24. PMID: 16618928 | PMCID: PMC1458901
  • Snook J, Li J, Helmke B, Guilford W. Peroxynitrite inhibits myofibrillar protein function in an in vitro assay of motility. Free radical biology & medicine. 2007;44(1): 14-23. PMID: 18045543 | PMCID: PMC2180163
  • Mott R, Helmke B. Mapping the dynamics of shear stress-induced structural changes in endothelial cells. American journal of physiology. Cell physiology. 2007;293(5): C1616-26. PMID: 17855768 | PMCID: PMC2746721
  • Yang W, Read P, Mi J, Baisden J, Reardon K, Larner J, Helmke B, Sheng K. Semiconductor nanoparticles as energy mediators for photosensitizer-enhanced radiotherapy. International journal of radiation oncology, biology, physics. 2008;72(3): 633-5. PMID: 19014777
  • Lin X, Helmke B. Micropatterned structural control suppresses mechanotaxis of endothelial cells. Biophysical journal. 2008;95(6): 3066-78. PMID: 18586851 | PMCID: PMC2527245
  • Huang L, Mathieu P, Helmke B. A stretching device for high-resolution live-cell imaging. Annals of biomedical engineering. 2010;38(5): 1728-40. PMID: 20195762 | PMCID: PMC3468334
  • Choi C, Helmke B. Short-Term Shear Stress Induces Rapid Actin Dynamics in Living Endothelial Cells. Molecular & cellular biomechanics : MCB. 2010;5(4): 247-258. PMID: 20084179 | PMCID: PMC2806644
  • Huang L, Helmke B. A Semi-Automatic Method for Image Analysis of Edge Dynamics in Living Cells. Cellular and molecular bioengineering. 2011;4(2): 205-219. PMID: 21643526 | PMCID: PMC3105629