May the force be with you
Biophysical cues such as biomaterial nanoscale stiffness and biomechanical forces have only recently emerged as essential determinants of cell fate, which can be equally important as biochemical and genetic factors. Acknowledging this, one uses terms such as the “rise of mechano-transduction”, “mechano-transduction: use the force”, and “mechano-transduction: may the force be with you”.
These biophysical cues have in common that they modulate the balance between extracellular and intracellular forces, alter cytoskeleton stress and cellular shape, and, importantly, also the associated cell function. Bernd and his team have demonstrated that cell shape and function are controlled by biomaterial surface nanoscale stiffnesses and biomechanical forces such as cyclic stretch. In turn, they demonstrated that that a range of distinct cell shapes can intentionally be engineered by choosing specific stiffnesses and by using specific tensile forces.
Dissect these processes, Bernd and his team have set up a cell stimulation system, which combines two competing biophysical cues: cyclic stretch with dynamic effects on cell shape and nanoscale stiffness of the used biomaterial with static effects on cell shape. This unraveled that the biomechanical effects on cell shape were more effective than stiffness but the effects were also transient; ultimately, cell shape reversed back to the shape dictated by biomaterial properties. Moving forward, a promising application of this insight is to develop shape-instructive biomaterials that offer nanoscale cues and that transduce the dynamic in vivo biomechanical environment into specific MSC shapes for controlling MSC behavior.
Shaping the cell and the future: recent advancements in biophysical aspects relevant to regenerative medicine. Hart ML, Lauer JC, Selig M, Hanak M, Walters B, Rolauffs B. Invited review. J. Funct. Morphol. Kinesiol. 2018, 3(1), 2; doi:10.3390/jfmk3010002. (This article belongs to the Special Issue Selected Papers from TERMIS European Chapter Meeting 2017 on “Biomechanics, Morphology and Imaging”).
Engineering the geometrical shape of mesenchymal stromal cells through defined cyclic stretch regimens. Walters B, Uynuk-Ool T, Rothdiener M, Palm J, Hart ML, Stegemann JP, Rolauffs B. Sci Rep. 2017 Jul 26;7(1):6640 (IF: 5.228)
The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces. Uynuk-Ool T, Rothdiener M, Walters B, Hegemann M, Palm J, Nguyen P, Seeger T, Stöckle U, Stegemann JP, Aicher WK, Kurz B, Hart ML, Klein G, Rolauffs B *. J Tissue Eng Regen Med. 2017 Mar 29. doi: 10.1002/term.2263 (IF: 4.71)
Stretching human mesenchymal stromal cells on stiffness-customized collagen type I generates a smooth muscle marker profile without growth factor addition. Rothdiener M, Hegemann M, Uynuk-Ool T, Walters B, Papugy P, Nguyen P, Claus V, Seeger T, Stoeckle U, Stegemann JP, Aicher WK, Hart ML, Kurz B, Klein G, Rolauffs B. Sci Rep. 2016 Oct 24;6:35840 (IF: 5.228)
Meet the team
Professor Bernd Rolauffs, M.D.
Director of the G.E.R.N. Research Center
Section Head, Translational Medicine for Cell-Based Therapies
Univ.-Professor in Tissue Replacement
Dept. of Orthopedics and Trauma Surgery, Freiburg University Medical Center
Habilitation at the Eberhard Karls University of Tübingen
Doctor in Medicine, Medical School in Münster, Germany
Dept. of Biochemistry, Rush University, Chicago, USA
Massachusetts Institute of Technology, Center for Biomedical Engineering, Boston, USA
Tübingen University Medical Center and BG Trauma Center Tübingen, Germany
Münster University Medical Center, Germany
Sunderland Royal Hospital, UK