Torques within and outside the human spindle balance twist at anaphase.

At each cell division, nanometer-scale motors and microtubules give rise to the micron-scale spindle. Many mitotic motors step helically around microtubules in vitro, and most are predicted to twist the spindle in a left-handed direction. However, the human spindle exhibits only slight global twist, raising the question of how these molecular torques are balanced. Here, we find that anaphase spindles in the epithelial cell line MCF10A have a high baseline twist, and we identify factors that both increase and decrease this twist. The midzone motors KIF4A and MKLP1 are together required for left-handed twist at anaphase, and we show that KIF4A generates left-handed torque in vitro. The actin cytoskeleton also contributes to left-handed twist, but dynein and its cortical recruitment factor LGN counteract it. Together, our work demonstrates that force generators regulate twist in opposite directions from both within and outside the spindle, preventing strong spindle twist during chromosome segregation.

Torques within and outside the human spindle balance twist at anaphase.

At each cell division, nanometer-scale motors and microtubules give rise to the micron-scale spindle. Many mitotic motors step helically around microtubules in vitro, and most are predicted to twist the spindle in a left-handed direction. However, the human spindle exhibits only slight global twist, raising the question of how these molecular torques are balanced. Here, using lattice light sheet microscopy, we find that anaphase spindles in the epithelial cell line MCF10A have a high baseline twist, and we identify factors that both increase and decrease this twist. The midzone motors KIF4A and MKLP1 are redundantly required for left-handed twist at anaphase, and we show that KIF4A generates left-handed torque in vitro. The actin cytoskeleton also contributes to left-handed twist, but dynein and its cortical recruitment factor LGN counteract it. Together, our work demonstrates that force generators regulate twist in opposite directions from both within and outside the spindle, preventing strong spindle twist during chromosome segregation.

Perilacunar bone tissue exhibits sub-micrometer modulus gradation which depends on the recency of osteocyte bone formation in both young adult and early-old-age female C57Bl/6 mice.

Osteocytes resorb and replace bone local to the lacunar-canalicular system (LCS). However, whether osteocyte remodeling impacts bone quality adjacent to the LCS is not understood. Further, while aging is well-established to decrease osteocyte viability and truncate LCS geometry, it is unclear if aging also decreases perilacunar bone quality. To address these questions, we employed atomic force microscopy (AFM) to generate nanoscale-resolution modulus maps for cortical femur osteocyte lacunae from young (5-month) and early-old-age (22-month) female C57Bl/6 mice. AFM-mapped lacunae were also imaged with confocal laser scanning microscopy to determine which osteocytes recently deposited bone as determined by the presence of fluorochrome labels administered 2d and 8d before euthanasia. Modulus gradation with distance from the lacunar wall was compared for labeled (i.e., bone forming) and non-labeled lacunae in both young and aged mice. All mapped lacunae showed sub-microscale modulus gradation, with peak modulus values 200-400 nm from the lacunar wall. Perilacunar modulus gradations depended on the recency of osteocyte bone formation (i.e., the presence of labels). For both ages, 2d-labeled perilacunar bone had lower peak and bulk modulus compared to non-labeled perilacunar bone. Lacunar length reduced with age, but lacunar shape and size were not strong predictors of modulus gradation. Our findings demonstrate for the first time that osteocyte perilacunar remodeling impacts bone tissue modulus, one contributor to bone quality. Given the immense scale of the LCS, differences in perilacunar modulus resulting from osteocyte remodeling activity may affect the quality of a substantial amount of bone tissue.

Dynamically Tunable Friction via Subsurface Stiffness Modulation.

Currently soft robots primarily rely on pneumatics and geometrical asymmetry to achieve locomotion, which limits their working range, versatility, and other untethered functionalities. In this paper, we introduce a novel approach to achieve locomotion for soft robots through dynamically tunable friction to address these challenges, which is achieved by subsurface stiffness modulation (SSM) of a stimuli-responsive component within composite structures. To demonstrate this, we design and fabricate an elastomeric pad made of polydimethylsiloxane (PDMS), which is embedded with a spiral channel filled with a low melting point alloy (LMPA). Once the LMPA strip is melted upon Joule heating, the compliance of the composite structure increases and the friction between the composite surface and the opposing surface increases. A series of experiments and finite element analysis (FEA) have been performed to characterize the frictional behavior of these composite pads and elucidate the underlying physics dominating the tunable friction. We also demonstrate that when these composite structures are properly integrated into soft crawling robots inspired by inchworms and earthworms, the differences in friction of the two ends of these robots through SSM can potentially be used to generate translational locomotion for untethered crawling robots.