Controlling Organization and Forces in Active Matter Through Optically-Defined Boundaries

Living systems are capable of locomotion, reconfiguration, and replication. To perform these tasks, cells spatiotemporally coordinate the interactions of force-generating, "active" molecules that create and manipulate non-equilibrium structures and force fields that span up to millimeter length scales [1-3]. Experimental active matter systems of biological or synthetic molecules are capable of spontaneously organizing into structures [4,5] and generating global flows [6-9]. However, these experimental systems lack the spatiotemporal control found in cells, limiting their utility for studying non-equilibrium phenomena and bioinspired engineering. Here, we uncover non-equilibrium phenomena and principles by optically controlling structures and fluid flow in an engineered system of active biomolecules. Our engineered system consists of purified microtubules and light-activatable motor proteins that crosslink and organize microtubules into distinct structures upon illumination. We develop basic operations, defined as sets of light patterns, to create, move, and merge microtubule structures. By composing these basic operations, we are able to create microtubule networks that span several hundred microns in length and contract at speeds up to an order of magnitude faster than the speed of an individual motor. We manipulate these contractile networks to generate and sculpt persistent fluid flows. The principles of boundary-mediated control we uncover may be used to study emergent cellular structures and forces and to develop programmable active matter devices

No Veteran Left Behind

This Co-Learning Plan analyzed the demographics of returning veterans and military retirees, the range of skills these vets possess and the most common obstacles they will encounter. A list of programs serving veterans by state, including financing, training, assistance, etc. was compiled. Lastly, success stories of veterans who have overcome obstacles to find new niches for themselves were used to document and recommend best practices for helping veterans re-enter the workforce

Syndecan 4 is Required for Endothelial Alignment in Flow and Atheroprotective Signaling

Atherosclerotic plaque localization correlates with regions of disturbed flow in which endothelial cells (ECs) align poorly, whereas sustained laminar flow correlates with cell alignment in the direction of flow and resistance to atherosclerosis. We now report that in hypercholesterolemic mice, deletion of syndecan 4 (S4−/−) drastically increased atherosclerotic plaque burden with the appearance of plaque in normally resistant locations. Strikingly, ECs from the thoracic aortas of S4−/− mice were poorly aligned in the direction of the flow. Depletion of S4 in human umbilical vein endothelial cells (HUVECs) using shRNA also inhibited flow-induced alignment in vitro, which was rescued by re-expression of S4. This effect was highly specific, as flow activation of VEGF receptor 2 and NF-κB was normal. S4-depleted ECs aligned in cyclic stretch and even elongated under flow, although nondirectionally. EC alignment was previously found to have a causal role in modulating activation of inflammatory versus antiinflammatory pathways by flow. Consistent with these results, S4-depleted HUVECs in long-term laminar flow showed increased activation of proinflammatory NF-κB and decreased induction of antiinflammatory kruppel-like factor (KLF) 2 and KLF4. Thus, S4 plays a critical role in sensing flow direction to promote cell alignment and inhibit atherosclerosis

Controlling Organization and Forces in Active Matter Through Optically-Defined Boundaries

Living systems are capable of locomotion, reconfiguration and replication. To perform these tasks, cells spatiotemporally coordinate the interactions of force-generating, ‘active’ molecules that create and manipulate non-equilibrium structures and force fields of up to millimetre length scales. Experimental active-matter systems of biological or synthetic molecules are capable of spontaneously organizing into structures and generating global flows. However, these experimental systems lack the spatiotemporal control found in cells, limiting their utility for studying non-equilibrium phenomena and bioinspired engineering. Here we uncover non-equilibrium phenomena and principles of boundary-mediated control by optically modulating structures and fluid flow in an engineered system of active biomolecules. Our system consists of purified microtubules and light-activatable motor proteins that crosslink and organize the microtubules into distinct structures upon illumination. We develop basic operations—defined as sets of light patterns—to create, move and merge the microtubule structures. By combining these operations, we create microtubule networks that span several hundred micrometres in length and contract at speeds up to an order of magnitude higher than the speed of an individual motor protein. We manipulate these contractile networks to generate and sculpt persistent fluid flows. The principles of boundary-mediated control that we uncover may be used to study emergent cellular structures and forces and to develop programmable active-matter devices

How to Advance Legal Education for Future Public Health Professionals.

Recent scholarship has advocated for schools and programs of public health (SPPHs) to move public health law from the periphery to the core of the public health curriculum, in recognition of law’s role as a fundamental driver of health outcomes. 1,2 The Five Essential Public Health Law Services—developed through a transdisciplinary collaboration of public health practitioners, researchers, advocates, and attorneys—emphasize that competency in public health law requires much more than the ability to summarize key statutes or court decisions.3 Rather, “[p]eople working in public health—whether in agencies, non-governmental organizations, health systems, research and even biomedical sciences— can expect to carry out a variety of functions that involve law, frequently without the assistance or even the involvement of lawyers.”1 These functions include the design, development, implementation, enforcement, and evaluation of legal interventions (to prevent drug overdoses, ensure food safety, contain infectious disease outbreaks, and much more)—functions that have become more complex and politically charged, but no less important, since the onset of the COVID-19 pandemic

Hydrodynamic Hunters

The Gram-negative Bdellovibrio bacteriovorus (BV) is a model bacterial predator that hunts other bacteria and may serve as a living antibiotic. Despite over 50 years since its discovery, it is suggested that BV probably collides into its prey at random. It remains unclear to what degree, if any, BV uses chemical cues to target its prey. The targeted search problem by the predator for its prey in three dimensions is a difficult problem: it requires the predator to sensitively detect prey and forecast its mobile prey’s future position on the basis of previously detected signal. Here instead we find that rather than chemically detecting prey, hydrodynamics forces BV into regions high in prey density, thereby improving its odds of a chance collision with prey and ultimately reducing BV’s search space for prey. We do so by showing that BV’s dynamics are strongly influenced by self-generated hydrodynamic flow fields forcing BV onto surfaces and, for large enough defects on surfaces, forcing BV in orbital motion around these defects. Key experimental controls and calculations recapitulate the hydrodynamic origin of these behaviors. While BV’s prey (Escherichia coli) are too small to trap BV in hydrodynamic orbit, the prey are also susceptible to their own hydrodynamic fields, substantially confining them to surfaces and defects where mobile predator and prey density is now dramatically enhanced. Colocalization, driven by hydrodynamics, ultimately reduces BV’s search space for prey from three to two dimensions (on surfaces) even down to a single dimension (around defects). We conclude that BV’s search for individual prey remains random, as suggested in the literature, but confined, however—by generic hydrodynamic forces—to reduced dimensionality