Control of cell behaviour through nanovibrational stimulation: nanokicking

Abstract

Mechanical signals are ubiquitous in our everyday life and the process of converting these mechanical signals into a biological signalling response is known as mechanotransduction. Our understanding of mechanotransduction, and its contribution to vital cellular responses, is a rapidly expanding field of research involving complex processes that are still not clearly understood. The use of mechanical vibration as a stimulus of mechanotransduction, including variation of frequency and amplitude, allows an alternative method to control specific cell behaviour without chemical stimulation (e.g. growth factors). Chemical-independent control of cell behaviour could be highly advantageous for fields including drug discovery and clinical tissue engineering. In this review, a novel technique is described based on nanoscale sinusoidal vibration. Using finite-element analysis in conjunction with laser interferometry, techniques that are used within the field of gravitational wave detection, optimization of apparatus design and calibration of vibration application have been performed. We further discuss the application of nanovibrational stimulation, or ‘nanokicking’, to eukaryotic and prokaryotic cells including the differentiation of mesenchymal stem cells towards an osteoblast cell lineage. Mechanotransductive mechanisms are discussed including mediation through the Rho-A kinase signalling pathway. Optimization of this technique was first performed in two-dimensional culture using a simple vibration platform with an optimal frequency and amplitude of 1 kHz and 22 nm. A novel bioreactor was developed to scale up cell production, with recent research demonstrating that mesenchymal stem cell differentiation can be efficiently triggered in soft gel constructs. This important step provides first evidence that clinically relevant (three-dimensional) volumes of osteoblasts can be produced for the purpose of bone grafting, without complex scaffolds and/or chemical induction. Initial findings have shown that nanovibrational stimulation can also reduce biofilm formation in a number of clinically relevant bacteria. This demonstrates additional utility of the bioreactor to investigate mechanotransduction in other fields of research.This article is part of a discussion meeting issue ‘The promises of gravitational-wave astronomy’.

Fracture Non-Union: A Review of Clinical Challenges and Future Research Needs

“…The ability of MSCs to differentiate in a number of cell lineages including osteoblasts has been harnessed by mechanotransductive technologies focussed on bone regeneration. External physical stimuli including hypergravity, shear forces and compressive loading have all been shown to be inducers of MSC differentiation 55 . Exposure of rat MSCs to a hypergravity environment induced upregulation of osteogenic markers both at protein and gene level, as well as changes to cell morphology and shape suggesting enhancement of the osteogenic differentiation of MSCs 56 .…”

Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

“…Due to the growing interest in mechanotransduction as a method to control cell behaviour and stem cell differentiation, the authors are developing a new power supply unit that can deliver a broader range of user-defined frequencies (1 Hz to 5 kHz) and amplitudes (up to 100 nm). If cellular nanoscale mechanotransduction/mechanosensing has indeed developed early within evolutionary history, as suggested by the bacterial studies conducted 45 , then further exploitation of the bioreactor technology is highly likely. Thus, an entirely new field of mechanobiology may be opened.…”

Design, construction and characterisation of a novel nanovibrational bioreactor and cultureware for osteogenesis

“…Due to the growing interest in mechanotransduction as a method to control cell behaviour and stem cell differentiation, the authors are developing a new power supply unit that can deliver a broader range of user-defined frequencies (1 Hz to 5 kHz) and amplitudes (up to 100 nm). If cellular nanoscale mechanotransduction/ mechanosensing has indeed developed early within evolutionary history, as suggested by the bacterial studies conducted 45 , then further exploitation of the bioreactor technology is Figure 8. Protein expression at three weeks of nanovibrational stimulation.…”