Magnetic microposts as an approach to apply forces to living cells

Abstract

Cells respond to mechanical forces whether applied externally or generated internally via the cytoskeleton. To study the cellular response to forces separately, we applied external forces to cells via microfabricated magnetic posts containing cobalt nanowires interspersed among an array of elastomeric posts, which acted as independent sensors to cellular traction forces. A magnetic field induced torque in the nanowires, which deflected the magnetic posts and imparted force to individual adhesions of cells attached to the array. Using this system, we examined the cellular reaction to applied forces and found that applying a step force led to an increase in local focal adhesion size at the site of application but not at nearby nonmagnetic posts. Focal adhesion recruitment was enhanced further when cells were subjected to multiple force actuations within the same time interval. Recording the traction forces in response to such force stimulation revealed two responses: a sudden loss in contractility that occurred within the first minute of stimulation or a gradual decay in contractility over several minutes. For both types of responses, the subcellular distribution of loss in traction forces was not confined to locations near the actuated micropost, nor uniformly across the whole cell, but instead occurred at discrete locations along the cell periphery. Together, these data reveal an important dynamic biological relationship between external and internal forces and demonstrate the utility of this microfabricated system to explore this interaction.focal adhesions ͉ magnetic nanowires ͉ mechanotransduction ͉ microfabrication ͉ traction forces

Magnetic approaches to study collective three-dimensional cell mechanics in long-term cultures (invited)

“…13 Magneto-mechanical actuation has been used as an effective method to introduce mechanical stimulation to single cells in studies of mechanotransduction. 11,[14][15][16][17][18][19] The extension of this technique to microtissues in the current study enables simultaneous measurement of both the contractile force and the tissue stiffness. Using this integrated magnetic microtissue tester (MMT) system, we decoupled the cell and ECM contributions to the contraction force and the stiffness of microtissues subjected to short culture periods (up to three days).…”

“…These include the advent of two-dimensional (2D) substrates for cell culture that spans a range of physiologic stiffnesses 3,7 that can be used to apply force to cells, and whose deformations can be used to report cellular forces. [8][9][10][11] However, despite their utility, these tools are not well suited to address the broader field of tissue remodeling and morphogenesis because the complex reorganization and deformations that occur in 3D are not captured in these 2D settings.…”

Whole cell mechanics of contractile fibroblasts: relations between effective cellular and extracellular matrix moduli

“…Each of these suffers from uncertainty owing to lack of connection to the natural structural network of a cell, and the reported values for the effective 'elastic modulus' of a cell range from 0.0002 to 0.1 MPa using these approaches. Although the patterning of cells onto substrates containing magnetically actuated, micropatterned ligand patches on elastic posts presents excellent data on cell forces, whole cell moduli cannot be deduced readily from these experiments (Sniadecki et al 2007).…”

Magnetically actuated cell-laden microscale hydrogels for probing strain-induced cell responses in three dimensions

“…[18][19][20] In these systems, 3D microtissues were created and constrained between patterned poly(dimethylsiloxane) cantilevers attached to a magnetically responsive microsphere. Such microtissue force gauges have allowed fast diffusion of soluble factors to multiple samples simultaneously, offered the capability to apply external mechanical loading to the specimens and enabled measurement of the contractility of multicellular tissues under applied force.…”