Matrix viscoplasticity and its shielding by active mechanics in microtissue models: experiments and mathematical modeling.

The biomechanical behavior of tissues under mechanical stimulation is critically important to physiological function. We report a combined experimental and modeling study of bioengineered 3D smooth muscle microtissues that reveals a previously unappreciated interaction between active cell mechanics and the viscoplastic properties of the extracellular matrix. The microtissues' response to stretch/unstretch actuations, as probed by microcantilever force sensors, was dominated by cellular actomyosin dynamics. However, cell lysis revealed a viscoplastic response of the underlying model collagen/fibrin matrix. A model coupling Hill-type actomyosin dynamics with a plastic perfectly viscoplastic description of the matrix quantitatively accounts for the microtissue dynamics, including notably the cells' shielding of the matrix plasticity. Stretch measurements of single cells confirmed the active cell dynamics, and were well described by a single-cell version of our model. These results reveal the need for new focus on matrix plasticity and its interactions with active cell mechanics in describing tissue dynamics.

A microfabricated magnetic actuation device for mechanical conditioning of arrays of 3D microtissues.

This paper describes an approach to actuate magnetically arrays of microtissue constructs for long-term mechanical conditioning and subsequent biomechanical measurements. Each construct consists of cell/matrix material self-assembled around a pair of flexible poly(dimethylsiloxane) (PDMS) pillars. The deflection of the pillars reports the tissues' contractility. Magnetic stretching of individual microtissues via magnetic microspheres mounted on the cantilevers has been used to elucidate the tissues' elastic modulus and response to varying mechanical boundary conditions. This paper describes the fabrication of arrays of micromagnetic structures that can transduce an externally applied uniform magnetic field to actuate simultaneously multiple microtissues. These structures are fabricated on silicon-nitride coated Si wafers and contain electrodeposited Ni bars. Through-etched holes provide optical and culture media access when the devices are mounted on the PDMS microtissue scaffold devices. Both static and AC forces (up to 20 µN on each microtissue) at physiological frequencies are readily generated in external fields of 40 mT. Operation of the magnetic arrays was demonstrated via measurements of elastic modulus and dynamic stiffening in response to AC actuation of fibroblast populated collagen microtissues.