Periodic migration in a physical model of cells on micropatterns

We extend a model for the morphology and dynamics of a crawling eukaryotic cell to describe cells on micropatterned substrates. This model couples cell morphology, adhesion, and cytoskeletal flow in response to active stresses induced by actin and myosin. We propose that protrusive stresses are only generated where the cell adheres, leading to the cell's effective confinement to the pattern. Consistent with experimental results, simulated cells exhibit a broad range of behaviors, including steady motion, turning, bipedal motion, and periodic migration, in which the cell crawls persistently in one direction before reversing periodically. We show that periodic motion emerges naturally from the coupling of cell polarization to cell shape by reducing the model to a simplified one-dimensional form that can be understood analytically.Comment: 15 pages (includes supplementary material as an appendix). Recently accepted to Physical Review Letter

Microspine Gripping Mechanism for Asteroid Capture

This paper details the development and early testing of a compliant suspension for a microspine gripper device for asteroid capture or micro-gravity percussive drilling. The microspine gripper architecture is reviewed, and a proposed microspine suspension design is presented and discussed. Prototyping methods are discussed, as well as testing methods and results. A path forward is identified from the results of the testing completed thus far. Key findings include: the microspine concept has been established as a valid architecture and the compliant suspension exhibits the desired stiffness characteristics for good gripping behavior. These developments will aid in developing the capability to grasp irregularly shaped boulders in micro-gravity

Viral Packaging ATPases Utilize a Glutamate Switch to Couple ATPase Activity and DNA Translocation [preprint]

Many viruses utilize ringed packaging ATPases to translocate double-stranded DNA into procapsids during replication. A critical step in the mechanochemical cycle of such ATPases is ATP binding, which causes a subunit within the motor to grip DNA tightly. Here, we probe the underlying molecular mechanism by which ATP binding is coupled to DNA gripping and show that a glutamate switch residue found in AAA+ enzymes is central to this coupling in viral packaging ATPases. Using free energy landscapes computed through molecular dynamics simulations, we determined the stable conformational state of the ATPase active site in apo, ATP-bound, and ADP-bound states. Our results show that the catalytic glutamate residue transitions from an inactive to an active pose upon ATP binding, and that a residue assigned as the glutamate switch is necessary for regulating the transition. Further, we identified via mutual information analyses the intramolecular signaling pathway mediated by the glutamate switch that is responsible for coupling ATP binding to conformational transitions of DNA-gripping motifs. We corroborated these predictions with both structural and functional experimental data. Specifically, we showed that the crystal structure of the ADP-bound P74-26 packaging ATPase is consistent with the predicted structural coupling from simulations, and we further showed that disrupting the predicted signaling pathway indeed decouples ATPase activity from DNA translocation activity in the φ29 DNA packaging motor. Our work thus establishes a signaling pathway in viral DNA packaging motors that ensures coordination between chemical and mechanical events involved in viral DNA packaging

A Brownian ratchet model for DNA loop extrusion by the cohesin complex.

The cohesin complex topologically encircles DNA to promote sister chromatid cohesion. Alternatively, cohesin extrudes DNA loops, thought to reflect chromatin domain formation. Here, we propose a structure-based model explaining both activities. ATP and DNA binding promote cohesin conformational changes that guide DNA through a kleisin N-gate into a DNA gripping state. Two HEAT-repeat DNA binding modules, associated with cohesin’s heads and hinge, are now juxtaposed. Gripping state disassembly, following ATP hydrolysis, triggers unidirectional hinge module movement, which completes topological DNA entry by directing DNA through the ATPase head gate. If head gate passage fails, hinge module motion creates a Brownian ratchet that, instead, drives loop extrusion. Molecular-mechanical simulations of gripping state formation and resolution cycles recapitulate experimentally observed DNA loop extrusion characteristics. Our model extends to asymmetric and symmetric loop extrusion, as well as z-loop formation. Loop extrusion by biased Brownian motion has important implications for chromosomal cohesin function

Blood Oxygenation Level-Dependent Response to Multiple Grip Forces in Multiple Sclerosis: Going Beyond the Main Effect of Movement in Brodmann Area 4a and 4p

This study highlights the importance of looking beyond the main effect of movement to study alterations in functional response in the presence of central nervous system pathologies such as multiple sclerosis (MS). Data show that MS selectively affects regional BOLD (blood oxygenation level dependent) responses to variable grip forces (GF). It is known that the anterior and posterior BA 4 areas (BA 4a and BA 4p) are anatomically and functionally distinct. It has also been shown in healthy volunteers that there are linear (first order, typical of BA 4a) and nonlinear (second to fourth order, typical of BA 4p) BOLD responses to different levels of GF applied during a dynamic motor paradigm. After modeling the BOLD response with a polynomial expansion of the applied GFs, the particular case of BA 4a and BA 4p were investigated in healthy volunteers (HV) and MS subjects. The main effect of movement (zeroth order) analysis showed that the BOLD signal is greater in MS compared with healthy volunteers within both BA 4 subregions. At higher order, BOLD-GF responses were similar in BA 4a but showed a marked alteration in BA 4p of MS subjects, with those with greatest disability showing the greatest deviations from the healthy response profile. Therefore, the different behaviors in HV and MS could only be uncovered through a polynomial analysis looking beyond the main effect of movement into the two BA 4 subregions. Future studies will investigate the source of this pathophysiology, combining the present fMRI paradigm with blood perfusion and nonlinear neuronal response analysis

Effects of residual charge on the performance of electro-adhesive grippers

Electro-adhesion is the new technology for constructing gripping solutions that can be used for automation of pick and place of a variety of materials. Since the technology works on the principle of parallel plate capacitors, there is an inherent ability to store charge when high voltage is applied. This causes an increased release time of the substrate when the voltage is switched off. This paper addresses the issue of residual charge and suggests ways to overcome the same, so that the performance of the gripper can be improved in a cycle of pick and release. Also a new universal equation has been devised, that can be used to calculate the performance of any gripping solution. This equation has been used to define a desired outcome (K) that has been evaluated for different configurations of the suggested electro-adhesive gripper

The Etiology of Thumb Carpometacarpal Osteoarthritis: Early Indications from In Vivo Joint Contact Mechanics

The thumb carpometacarpal (CMC) joint is frequently affected by osteoarthritis (OA). The prevalence of thumb CMC OA greatly increases with age and has disproportional predominance in postmenopausal women. However, so far the etiology of thumb CMC OA remains unclear, and no conclusion has been achieved regarding the selection of the optimal surgical procedure. Joint contact mechanics can be an important aspect in understanding the mechanism of thumb CMC OA development. The contact pressure distribution on the articular surface directly affects the cartilage condition. This study quantitatively compared the in vivo thumb CMC joint contact mechanics between 4 males and 4 females using finite element modeling (FEM), and also evaluated the accuracy of a time-efficient surface-based contact modeling (SCM) procedure for possible clinical application. Although a sufficient statistical power cannot be achieved with the small number of subjects, the contact patterns were substantially different between male and female groups. Contact area, force and peak contact pressure showed a trend of increase in the older female subjects. Compared with FEM, the contact parameter values from SCM may be somewhat less accurate, but SCM produced contact distribution patterns similar to FEM. In addition, SCM was able to distinguish the different contact patterns between normal and osteoarthritic thumb CMC joints with much less data processing. Therefore, SCM has clear potential for future clinical diagnosis and the evaluation of treatment efficacy for thumb CMC OA

Performance evaluation of a six-axis generalized force-reflecting teleoperator

Work in real-time distributed computation and control has culminated in a prototype force-reflecting telemanipulation system having a dissimilar master (cable-driven, force-reflecting hand controller) and a slave (PUMA 560 robot with custom controller), an extremely high sampling rate (1000 Hz), and a low loop computation delay (5 msec). In a series of experiments with this system and five trained test operators covering over 100 hours of teleoperation, performance was measured in a series of generic and application-driven tasks with and without force feedback, and with control shared between teleoperation and local sensor referenced control. Measurements defining task performance included 100-Hz recording of six-axis force/torque information from the slave manipulator wrist, task completion time, and visual observation of predefined task errors. The task consisted of high precision peg-in-hole insertion, electrical connectors, velcro attach-de-attach, and a twist-lock multi-pin connector. Each task was repeated three times under several operating conditions: normal bilateral telemanipulation, forward position control without force feedback, and shared control. In shared control, orientation was locally servo controlled to comply with applied torques, while translation was under operator control. All performance measures improved as capability was added along a spectrum of capabilities ranging from pure position control through force-reflecting teleoperation and shared control. Performance was optimal for the bare-handed operator