Review Mechanostasis in apoptosis and medicine D.D. Chan a, 1 , W.S. Van Dyke a , M. Bahls b , S.D. Connell a , P. Critser a , J.E. Kelleher c , M.A. Kramer a , S.M. Pearce a , S. Sharma a , C.P. Neu a, * a Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, United States b Department of Health and Kinesiology, Purdue University, West Lafayette, IN 47907, United States c School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, United States article info Article history: Available online 8 August 2011 Keywords: Apoptosis Programmed cell death Mechanobiology Shear stress/strain Mechanotransduction Homeostasis abstract Mechanostasis describes a complex and dynamic process where cells maintain equilibrium in response to mechanical forces. Normal physiological loading modes and magnitudes contribute to cell prolifera- tion, tissue growth, differentiation and development. However, cell responses to abnormal forces include compensatory apoptotic mechanisms that may contribute to the development of tissue disease and pathological conditions. Mechanotransduction mechanisms tightly regulate the cell response through discrete signaling pathways. Here, we provide an overview of links between pro- and anti-apoptotic signaling and mechanotransduction signaling pathways, and identify potential clinical applications for treatments of disease by exploiting mechanically-linked apoptotic pathways. Ó 2011 Elsevier Ltd. All rights reserved. Contents 1. Introduction ....................................................................................................................... 517 2. Mechanostasis: tissues adapt to physical cues ................................................ ......................................... 518 3. Programmed cell death ............................................................................................................. 519 4. Mechanotransduction and apoptosis .................................................... ............................................. 519 4.1. Extrinsic pathway ............................................................................................................ 519 4.2. Intrinsic pathway ............................................................................................................ 520 4.3. Caspase-independent cell death ............................................................................................... 521 4.4. Apoptotic pathway crosstalk .................................................................................................. 522 5. Mechanomedicine and apoptosis .................................................................................................... 522 6. Outlook .......................................................................................................................... 522 Conflict of interest ................................................................................................................. 523 Acknowledgments ............................................................ .................................................... 523 References ........................................................................................................................ 523 1. Introduction A paradox of morphogenesis is that programmed cell death is vital for the growth and maintenance of the living adult form. Apoptosis, a programmed cell death mechanism, is characterized by nuclear chromatin condensation, cytoplasmic vacuole forma- tion, and plasma membrane blebbing (Kresch et al., 1998). As the embryo matures, cells are removed by apoptosis to form joints and digitated appendices (Kimura and Shiota, 1996), to create airway branching for maximum surface area and gas exchange (Kresch et al., 1998), and to develop cardiac electrophysiology conduction systems (Poelmann and Gittenberger-de Groot, 1999). In postnatal organisms, a combination of mitosis and apoptosis maintains cell numbers with a turnover of approximately a hundred thousand cells each second (Vaux and Korsmeyer, 1999). Apoptosis is integral * Corresponding author. Tel.: þ1 765 496 1426; fax: þ1 765 494 0902. E-mail address: cpneu@purdue.edu (C.P. Neu). 1 First authorship was determined by a haiku writing competition that was judged by three unbiased faculty members. The winning haiku was: “Sensing outside force,/a cell shifts toward life or death./But which path to take?”. Contents lists available at ScienceDirect Progress in Biophysics and Molecular Biology journal homepage: www.elsevier.com/locate/pbiomolbio 0079-6107/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.pbiomolbio.2011.08.002 Progress in Biophysics and Molecular Biology 106 (2011) 517e524