Decoupling Cell and Matrix Mechanics in Engineered Microtissues Using Magnetically Actuated Microcantilevers

Abstract

A novel bio‐magnetomechanical microtissue system is described for magnetic actuation of arrays of 3D microtissues using microcantilevers. This system enables both in situ measurements of fundamental mechanical properties of engineered tissue, such as contractility and stiffness, as well as dynamic stimulation of the microtissues. Using this system, cell and extracellular matrix contributions to the tissue mechanical properties are decoupled for the first time under both static and dynamic loading conditions.

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

“…1(a)) via replica molding from molds made by two-layer microlithography, as previously described. 13 The PDMS used had elastic modulus 1.6 MPa, which yielded pillars with effective spring constant k ¼ 0.90 lN/lm for small deflections. A nickel sphere with $100 lm diameter was selected through visual screening from a group of nickel spheres with nominal diameter ranging from 74 lm to 116 lm (CAS 7440-02-0, À150þ200 mesh, Alfa Aesar), and was adhered to one pillar in each MMT.…”

“…The spontaneous contraction force F' ¼ kd' generated by a microtissue was determined from the average deflection d' of the two pillars in the MMT, as previously described. 13 To stretch a microtissue, the pole tip of the electromagnetic tweezer was immersed in the culture media and brought close to the edge of the MMT well (Figs. 1(c) and 1(d)), and a step-wise ramped magnetic field was applied to pull the magnetic pillar gradually towards the pole tip.…”

“…12 Furthermore, by integrating these microdevices with a magnetic actuation system, we were able to apply external loading to individual microtissues. 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.…”

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.…”

3D culture models of tissues under tension

“…Using a magnetic actuation platform and biochemical treatments to perturb cellular contractility, Zhao and colleagues have decoupled the contribution of cells and collagen to the overall stiffness of the microtissue in response to mechanical load (Zhao et al, 2013). Similar to changing the pillar stiffness, they found that under static load, the collagen matrix is the primary determinant of the tissue stiffness and that the cells adjust their own stiffness to match that of the matrix.…”