Key developments that impacted the field of mechanobiology and mechanotransduction

Abstract

Advances in mechanobiology have evolved through insights from multiple disciplines including structural engineering, biomechanics, vascular biology, and orthopaedics. In this paper, we reviewed the impact of key reports related to the study of applied loads on tissues and cells and the resulting signal transduction pathways. We addressed how technology has helped advance the burgeoning field of mechanobiology (over 33,600 publications from 1970 to 2016). We analyzed the impact of critical ideas and then determined how these concepts influenced the mechanobiology field by looking at the citation frequency of these reports as well as tracking how the overall number of citations within the field changed over time. These data allowed us to understand how a key publication, idea, or technology guided or enabled the field. Initial observations of how forces acted on bone and soft tissues stimulated the development of computational solutions defining how forces affect tissue modeling and remodeling. Enabling technologies, such as cell and tissue stretching, compression, and shear stress devices, allowed more researchers to explore how deformation and fluid flow affect cells. Observation of the cell as a tensegrity structure and advanced methods to study genetic regulation in cells further advanced knowledge of specific mechanisms of mechanotransduction. The future of the field will involve developing gene and drug therapies to simulate or augment beneficial load regimens in patients and in mechanically conditioning organs for implantation. Here, we addressed a history of the field, but we limited our discussions to advances in musculoskeletal mechanobiology, primarily in bone, tendon, and ligament tissues. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:605-619, 2018.

High shear stress amplitude in combination with prolonged stimulus duration determine induction of osteoclast formation by hematopoietic progenitor cells

“…This was summarized in a mathematical expression, where amplitude, frequency, duty cycle (loading duration, duration of resting phase), number of cycles, wall shear stress rate, wall shear stress, and substrate stiffness were discussed as potential critical factors for strain-induced responses on cells. 34 Although in these early observations the number of suggested contributing factors was quite large, we were able to formulate a simpler mathematical expression to describe the cellular response to a relatively wide range of fluid shear stresses, including loading amplitude and duty cycle. When applying the approximate area under the curve for square functions and error functions as a compound factor for loading amplitude and duration to explain the modulation of osteoclast formation, a strong correlation could be seen, suggesting that it is the combination of those two parameters that determine the directionality and strength of the osteoclast-modulating response.…”

Microfluidics for mechanobiology of model organisms

“…Physicians in the 19th century observed that bones can remodel their structure to support mechanical loads after a fracture (Wolff, 2010a, 2010b, 2011). More recently, Carter and Hayes (1976) continued this work and renewed the focus on mechanobiology of bone (reviewed by Carter, Beaupré, Giori, and Helms (1998) and Wall et al (2017)). The field has since expanded to study other tissues and cell types.…”

Vibration of osteoblastic cells using a novel motion‐control platform does not acutely alter cytosolic calcium, but desensitizes subsequent responses to extracellular ATP

“…The biological mechanisms underlying mechanotransduction are areas of intense study (Wall et al, 2017). In cells of the osteoblast lineage, early signaling events activated by mechanical stimuli such as fluid flow and membrane stretch include transient elevation in the concentration of cytosolic free calcium ([Ca 2+ ] i ) (Jing et al, 2014;Lorusso et al, 2016;Mikolajewicz, Zimmermann, Willie, & Komarova, 2018;Thi, Suadicani, Schaffler, Weinbaum, & Spray, 2013).…”