Abstract
The ability of cells to proliferate, differentiate, transduce extracellular signals and assemble tissues involves structural connections between nucleus and cytoskeleton. Yet, how the mechanics of these connections vary inside stem cells is not fully understood. To address those questions, we combined two-dimensional particle-tracking microrheology and morphological measures using variable reduction techniques to measure whether cytoplasmic mechanics allow for discrimination between different human adherent stem cell types and across different culture conditions. Here we show that nuclear shape is a quantifiable discriminant of mechanical properties in the perinuclear cytoskeleton (pnCSK) of various stem cell types. Also, we find the pnCSK is a region with different mechanical properties than elsewhere in the cytoskeleton, with heterogeneously distributed locations exhibiting subdiffusive features, and which obeys physical relations conserved among various stem cell types. Finally, we offer a prospective basis to discriminate between stem cell types by coupling perinuclear mechanical properties to nuclear shape.
Highlights
The ability of cells to perceive and respond to physical stimuli exists throughout development
Our hypothesis was that stem cells with different levels of multipotency–or “stemness”– show discernible cytoplasmic mechanics; in other words, we tested whether the mechanical properties inside the cytoplasm are practical measures that can discriminate between different stem cell phenotypes, in particular by asking if the mechanical properties inside the cytoplasm: a) captured the observed structural reorganization of the cytoskeleton after exposing stem cells to soluble cytokines or disrupting their actin polymerization pharmacologically in vitro; b) adapted differently to induced cytoskeletal remodeling when stem cell morphology was prescribed into a fixed geometry; and c) could distinguish among stem cells from different lineages
We reveal that the nuclear shape of stem cells scales the relations among orthotropic cytoplasmic mechanics near the nucleus
Summary
The ability of cells to perceive and respond to physical stimuli exists throughout development. Of progenitors to assemble physiologically sophisticated tissues, with complex multicellular makeup and spatially regulated architectures[18,35,36,37,38,39] Seen under this light, it seems clear that the cytoskeleton may show distinctive structural features among different stem cell types, yet we still ignore how these distinctions are expressed in the intracellular mechanics of stem cells or how can they be leveraged to discriminate stem cell lineages by physical cues. After determining associations between cytoplasmic mechanics in stem cells and their cytoskeleton, we examined if a combination of those mechanical properties followed a predictive relation common to stem cells from all experimental regimes–with the presumption that, if extant, such relations may hint at a structural foundation present in all stem cells
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