Desktop wax printer was employed to build high throughput platforms for studying stem cells fate.

Stiffness and forces are two fundamental quantities essential to living cells and tissues. However, it has been a challenge to quantify both 3D traction forces and stiffness (or modulus) using the same probe in vivo. Here, we describe an approach that overcomes this challenge by creating a magnetic microrobot probe with controllable functionality. Biocompatible ferromagnetic cobalt-platinum microcrosses were fabricated, and each microcross (about 30 micrometers) was trapped inside an arginine–glycine–apartic acid–conjugated stiff poly(ethylene glycol) (PEG) round microgel (about 50 micrometers) using a microfluidic device. The stiff magnetic microrobot was seeded inside a cell colony and acted as a stiffness probe by rigidly rotating in response to an oscillatory magnetic field. Then, brief episodes of ultraviolet light exposure were applied to dynamically photodegrade and soften the fluorescent nanoparticle–embedded PEG microgel, whose deformation and 3D traction forces were quantified. Using the microrobot probe, we show that malignant tumor–repopulating cell colonies altered their modulus but not traction forces in response to different 3D substrate elasticities. Stiffness and 3D traction forces were measured, and both normal and shear traction force oscillations were observed in zebrafish embryos from blastula to gastrula. Mouse embryos generated larger tensile and compressive traction force oscillations than shear traction force oscillations during blastocyst. The microrobot probe with controllable functionality via magnetic fields could potentially be useful for studying the mechanoregulation of cells, tissues, and embryos.

No abstract

Chromatin is a unique structure of DNA and histone proteins in the cell nucleus and the site of dynamic regulation of gene expression. Soluble factors are known to affect the chromatin structure and function via activating or inhibiting specific transcription factors. Forces on chromatin come from exogenous stresses on the cell surface and/or endogenous stresses, which are regulated by substrate mechanics, geometry, and topology. Forces on chromatin involve direct (via adhesion molecules, cytoskeleton, and the linker of nucleoskeleton and cytoskeleton complexes) and indirect (via diffusion and/or translocation processes) signaling pathways to modulate levels of chromatin folding and deformation to regulate transcription, which is controlled by histone modifications and depends on magnitude, direction, rate/frequency, duration, and modes of stresses. The rapid force transmission pathway activates multiple genes simultaneously, and the force may act like a “supertranscription factor.” The indirect mechanotransduction pathways and the rapid force transmission pathway together exert sustained impacts on the chromatin, the nucleus, and cell functions.