Magneto-active substrates for local mechanical stimulation of living cells

Abstract

Cells are able to sense and react to their physical environment by translating a mechanical cue into an intracellular biochemical signal that triggers biological and mechanical responses. This process, called mechanotransduction, controls essential cellular functions such as proliferation and migration. The cellular response to an external mechanical stimulation has been investigated with various static and dynamic systems, so far limited to global deformations or to local stimulation through discrete substrates. To apply local and dynamic mechanical constraints at the single cell scale through a continuous surface, we have developed and modelled magneto-active substrates made of magnetic micro-pillars embedded in an elastomer. Constrained and unconstrained substrates are analysed to map surface stress resulting from the magnetic actuation of the micro-pillars and the adherent cells. These substrates have a rigidity in the range of cell matrices, and the magnetic micro-pillars generate local forces in the range of cellular forces, both in traction and compression. As an application, we followed the protrusive activity of cells subjected to dynamic stimulations. Our magneto-active substrates thus represent a new tool to study mechanotransduction in single cells, and complement existing techniques by exerting a local and dynamic stimulation, traction and compression, through a continuous soft substrate.

Force-Mediating Magnetic Nanoparticles to Engineer Neuronal Cell Function

“…Distinct force applications at the cell membrane can be achieved through selective surface coatings on the nanoparticle (Calatayud et al, 2014 ; de Castro et al, 2018 ). Through forces acting on the cell membrane, cell protrusion can be initiated to start growing an axon in neurons (Fass and Odde, 2003 ; Ji et al, 2008 ; Betz et al, 2011 ; Diz-Muñoz et al, 2013 ; Pita-Thomas et al, 2015 ; Bidan et al, 2018 ). Extracellular forces at higher magnitudes can elongate neurites or growth cones (Bray, 1984 ; Zheng, 1991 ; Suter and Miller, 2011 ; Kilinc et al, 2015 ; Ren et al, 2018 ), guide cell displacement and migration, (Kunze et al, 2015 ; Doolin and Stroka, 2018 ; Van Helvert et al, 2018 ) or open membrane channels to interfere with neuronal cell communication (McBride and Hamill, 1993 ; Martinac, 2004 ; Morris and Juranka, 2007 ; Reeves et al, 2008 ; Beyder, 2010 ; Sanjeev Ranade et al, 2015 ; Tay et al, 2016a ).…”

Biomechanical Characterization at the Cell Scale: Present and Prospects

“…Moreover, they observed a global enhancement of cell traction forces following the application of a localized torque. Recently, Bidan et al (2018) applied a combination of MTs and TFM on deformable substrates enabling local and dynamic mechanical stimulation of cells plated on a continuous surface. Substrates consisted of a layer of soft elastomer embedding spatially arranged magnetic micropillars, that could be locally actuated by means of a MTs setup.…”

Hang on tight: reprogramming the cell with microstructural cues

“…To date, the ability to study the effect of mechanical load on living single cells has been limited by the need for high resolution spatial and temporal optical imaging in a realistic myocyte configuration. Attempts have been made using magnetically actuated micropost surfaces to provide forces along the underlying surface of a cell, but these do not mimic the type of three-dimensional strain experienced by cells in vivo (Bidan et al 2018; Sniadecki et al 2008). Microgroove-aligned CMs were cyclically strained using the Flexcell device, but these cells could not be imaged while mechanically deformed (Motlagh et al 2003; Senyo et al 2007).…”