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Abstract Living cells can adapt their shape in response to their environment, a process driven by the interaction between their flexible membrane and the activity of the underlying cytoskeleton. However, the precise physical mechanisms of this coupling remain unclear. Here we show how cytoskeletal forces acting on a biomimetic membrane affect its deformations. Using a minimal cell model that consists of an active network of microtubules and molecular motors encapsulated inside lipid vesicles, we observe large shape fluctuations and travelling membrane deformations. Quantitative analysis of membrane and microtubule dynamics demonstrates how active forces set the temporal scale of vesicle fluctuations, giving rise to fluctuation spectra that differ in both their spatial and temporal decays from their counterparts in thermal equilibrium. Using simulations, we extend the classical framework of membrane fluctuations to active cytoskeleton-driven vesicles, demonstrating how correlated activity governs membrane dynamics and the roles of confinement, membrane material properties and cytoskeletal forces. Our findings provide a quantitative foundation for understanding the shape-morphing abilities of living cells. 

Abstract A fragment‐based approach has proven successful in drug design and protein assemblies, yet its potential for constructing biomaterials from simple organic building blocks remains underexplored, particularly for self‐assembly in aqueous phases, where water disrupts intermolecular hydrogen bonding. To the best of our knowledge, this study introduces the first case of integrating fragments from self‐assembling molecules to design a small organic molecule that forms novel hierarchical nanotubes with polymorphism. The molecule's compact design incorporates three structural motifs derived from known nanotube assemblies, enabling a hierarchical assembly process: individual molecules with two conformations form dimers, which organize into hexameric units. These hexamers further assemble into nanotubes comprising 2‐, 5‐, and 6‐protofilament fibers. The nanofibers share a nearly identical asymmetric unit – a hexameric triangular plate – with similar axial and lateral interfaces. The lateral interface, involving interactions between phosphate groups and aromatic rings, exhibits plasticity, allowing slight rotational variations between adjacent units. This adaptability facilitates the formation of diverse nanofiber architectures, showcasing the flexibility of these systems in aqueous environments. By leveraging fragments of self‐assembling molecules, this work demonstrates a straightforward strategy that combines conformational flexibility and self‐assembling fragments to construct advanced supramolecular biomaterials from small organic building blocks in aqueous settings. 

Abstract While bond formation has historically been the mainstay of medicinal chemistry, the phenomenon of bond cleavage has received less focus. However, the success of numerous oral medications demonstrates the importance of controlled cleavage in prodrugs to achieve desired therapeutic outcomes. Nevertheless, effective strategies to control this cleavage remain limited. This concept article introduces a novel approach: employing peptides as conjugates to drugs to modulate the hydrolysis of these conjugates and enhance drug efficacy. The article begins by briefly outlining common prodrug strategies, followed by a few representative examples of how peptides can be leveraged to control the autohydrolysis of peptide‐conjugated prodrugs for bacterial and cancer cell inhibition. Finally, it provides a brief outlook on the future potential of this promising new research direction in molecular medicine. 

ABSTRACT Across the domains of life, actin homologs are integral components of many essential processes, such as DNA segregation, cell division, and cell shape determination. Archaeal genomes, like those of bacteria and eukaryotes, also encode actin homologs, but much less is known about these proteins’in vivodynamics and cellular functions. We identified and characterized the function and dynamics of Salactin, an actin homolog in the hypersaline archaeonHalobacterium salinarum. Live-cell time-lapse imaging revealed that Salactin forms dynamically unstable filaments that grow and shrink out of the cell poles. Like other dynamically unstable polymers, Salactin monomers are added at the growing filament end, and its ATP-bound critical concentration is substantially lower than the ADP-bound form. WhenH. salinarum’schromosomal copy number becomes limiting under low-phosphate growth conditions, cells lacking Salactin show perturbed DNA distributions. Taken together, we propose that Salactin is part of a previously unknown chromosomal segregation apparatus required during low-ploidy conditions. IMPORTANCEProtein filaments play important roles in many biological processes. We discovered an actin homolog in halophilic archaea, which we call Salactin. Just like the filaments that segregate DNA in eukaryotes, Salactin grows out of the cell poles towards the middle, and then quickly depolymerizes, a behavior known as dynamic instability. Furthermore, we see that Salactin affects the distribution of DNA in daughter cells when cells are grown in low-phosphate media, suggesting Salactin filaments might be involved in segregating DNA when the cell has only a few copies of the chromosome. 

Abstract Active processes drive biological dynamics across various scales and include subcellular cytoskeletal remodelling, tissue development in embryogenesis and the population-level expansion of bacterial colonies. In each of these, biological functionality requires collective flows to occur while self-organised structures are protected. However, the mechanisms by which active flows can spontaneously constrain their dynamics to preserve structure are not known. Here, by studying collective flows and defect dynamics in active nematic films, we demonstrate the existence of a self-constraint, namely a two-way, spontaneously arising relationship between activity-driven isosurfaces of flow boundaries and mesoscale nematic structures. We show that self-motile defects are tightly constrained to viscometric surfaces, which are contours along which the vorticity and the strain rate are balanced. This in turn reveals that self-motile defects break mirror symmetry when they move along a single viscometric surface. This is explained by an interdependence between viscometric surfaces and bend walls, which are elongated narrow kinks in the orientation field. These findings indicate that defects cannot be treated as solitary points. Instead, their associated mesoscale deformations are key to the steady-state coupling to hydrodynamic flows. This mesoscale cross-field self-constraint offers a framework for tackling complex three-dimensional active turbulence, designing dynamic control into biomimetic materials and understanding how biological systems can employ active stress for dynamic self-organisation. 

Abstract The intricate nature of eukaryotic cells with intracellular compartments having differences in component concentration and viscosity in their lumen provides (membrane‐active) enzymes to trigger time‐ and concentration‐dependent processes in the intra‐/extracellular matrix. Herein, membrane‐active, enzyme‐loaded artificial organelles (AOs) are capitalized upon to develop fluidic and stable proteinaceous membrane‐based protocells. AOs in protocells induce the self‐assembly of oligopeptides into an artificial cytoskeleton that underlines their influence on the structure and functionality of protocells. A series of microscopical tools is used to validate the intracellular assembly and distribution of cytoskeleton, the changing protocells morphology, and AOs inclusion within cytoskeletal growth. Thus, the dynamics, diffusion, and viscosity of intracellular components in the presence of cytoskeleton are evaluated by fluorescence tools and enzymatic assay. Membrane‐active alkaline phosphatase in polymersomes as AOs fulfills the requirements of biomimetic eukaryotic cells to trigger intracellular environment, mobility, viscosity, diffusion, and enzymatic activity itself as well as high mechanical stability and high membrane fluidity of protocells. Thus membrane‐active AOs in protocells provide a variable reaction space in a changing intracellular environment and underline their regulatory role in the fabrication of complex protocell architectures and functions. This study contributes significantly to the effective biomimetics of cell‐like structures, shapes, and functions. 

Abstract Rapid cellular uptake of synthetic molecules remains a challenge, and the motif frequently employed to generate prodrugs, succinic ester, unfortunately lowers the efficacy of the desired drugs due to their slow ester hydrolysis and low cell entry. Here we show that succinic ester‐containing diglycine drastically boosts the cellular uptake of supramolecular assemblies or prodrugs. Specifically, autohydrolysis of the diglycine‐activated succinic esters turns the nanofibers of the conjugates of succinic ester and self‐assembling motif into nanoparticles for fast cellular uptake. The autohydrolysis of diglycine‐activated succinic esters and drug conjugates also restores the efficacy of the drugs. 2D nuclear magnetic resonance (NMR) suggests that a “U‐turn” of diglycine favors intramolecular hydrolysis of diglycine‐activated succinic esters to promote autohydrolysis. As an example of rapid autohydrolysis of diglycine‐activated succinic esters for instant cellular uptake, this work illustrates a nonenzymatic bond cleavage approach to develop effective therapeutics for intracellular targeting. 

Abstract Photonic crystals—a class of materials whose optical properties derive from their structure in addition to their composition—can be created by self-assembling particles whose sizes are comparable to the wavelengths of visible light. Proof-of-principle studies have shown that DNA can be used to guide the self-assembly of micrometer-sized colloidal particles into fully programmable crystal structures with photonic properties in the visible spectrum. However, the extremely temperature-sensitive kinetics of micrometer-sized DNA-functionalized particles has frustrated attempts to grow large, monodisperse crystals that are required for photonic metamaterial applications. Here we describe a robust two-step protocol for self-assembling single-domain crystals that contain millions of optical-scale DNA-functionalized particles: Monodisperse crystals are initially assembled in monodisperse droplets made by microfluidics, after which they are grown to macroscopic dimensions via seeded diffusion-limited growth. We demonstrate the generality of our approach by assembling different macroscopic single-domain photonic crystals with metamaterial properties, like structural coloration, that depend on the underlying crystal structure. By circumventing the fundamental kinetic traps intrinsic to crystallization of optical-scale DNA-coated colloids, we eliminate a key barrier to engineering photonic devices from DNA-programmed materials. 

Abstract Much like passive materials, active systems can be affected by the presence of imperfections in their microscopic order, called defects, that influence macroscopic properties. This suggests the possibility to steer collective patterns by introducing and controlling defects in an active system. Here we show that a self-assembled, passive nematic is ideally suited to control the pattern formation process of an active fluid. To this end, we force microtubules to glide inside a passive nematic material made from actin filaments. The actin nematic features self-assembled half-integer defects that steer the active microtubules and lead to the formation of macroscopic polar patterns. Moreover, by confining the nematic in circular geometries, chiral loops form. We find that the exact positioning of nematic defects in the passive material deterministically controls the formation and the polarity of the active flow, opening the possibility of efficiently shaping an active material using passive defects. 

Significance Active forces sculpt the forms of living things, generating adaptable and reconfigurable dynamical materials. Creating synthetic materials that exhibit comparable control over internally generated active forces remains a challenge. We demonstrate that active composite networks, collectively driven by the force-generating molecular motors, exhibit complex spatiotemporal patterns similar to those observed in cell biology. Amongst others, we describe robust self-assembly of onion-like layered asters. A self-regulating mechanism ensures the asters’ layered structure survives coalescence-like events, while their temporal stability is encoded in the mechanical properties of the network. Our model system elucidates the essential role of passive elasticity in controlling the emergent nonequilibrium dynamics while also establishing a robust experimental platform for engineering lifelike materials.