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Consistent individual differences in behavior, known as behavioral individuality, are pervasive across the animal world and have major ecological and evolutionary consequences. Nevertheless, we still have a limited understanding of what drives individuality and how it emerges during ontogeny. Here, we subjected clonal individuals to a ubiquitous yet critical environmental challenge—the threat of predation—to disentangle the developmental mechanisms of individuality. Under such a salient environmental stressor, among-individual differences may collapse or expand depending on whether there is a single or multiple optimal strategies, demonstrating that individuality itself is a developmentally plastic trait. If, however, the environment does not impact among-individual variation, this suggests that individuality is determined before birth. We continuously tracked the behavior of genetically identical fish (Amazon mollies, Poecilia formosa), reared with or without predation stress, from birth through their first month of life. Predation shifted mean-level behaviors, with predator-exposed individuals swimming more slowly and spending more time near their refuges. However, the magnitude of individuality (as evidenced by repeatability) increased similarly over development in both treatments, indicating that individuality crystallizes robustly over time, even under stress and in a vacuum of genetic variation. Predator-reared fish also exhibited greater within-individual variability in refuge use, suggesting increased behavioral flexibility or disrupted developmental canalization in response to stress. Surprisingly, maternal identity, but not maternal behavior, was the strongest predictor of swimming speed, pointing to non-behavioral maternal effects as a key pre-birth source of behavioral variation. Refuge use however was not at all predicted by maternal identity, indicating that major fitness-related behaviors can have entirely different developmental mechanisms. Collectively, we show that individuality persists despite environmental stress and is seeded before birth through non-genetic factors. Even in the face of a shared environmental challenge, the behavioral trajectories of individuals are unique. 

Stress quantification can be observed during single fiber pull-out test in a polymer matrix composite with stress sensing molecules. 

Abstract Millions of years of evolution have optimized many biosynthetic pathways by use of multi‐step catalysis. In addition, multi‐step metabolic pathways are commonly found in and on membrane‐bound organelles in eukaryotic biochemistry. The fundamental mechanisms that facilitate these reaction processes provide strategies to bioengineer metabolic pathways in synthetic chemistry. Using Brownian dynamics simulations, here we modeled intermediate substrate transportation of colocalized yeast–ester biosynthesis enzymes on the membrane. The substrate acetate ion traveled from the pocket of aldehyde dehydrogenase to its target enzyme acetyl‐CoA synthetase, then the substrate acetyl CoA diffused from Acs1 to the active site of the next enzyme, alcohol‐O‐acetyltransferase. Arranging two enzymes with the smallest inter‐enzyme distance of 60 Å had the fastest average substrate association time as compared with anchoring enzymes with larger inter‐enzyme distances. When the off‐target side reactions were turned on, most substrates were lost, which suggests that native localization is necessary for efficient final product synthesis. We also evaluated the effects of intermolecular interactions, local substrate concentrations, and membrane environment to bring mechanistic insights into the colocalization pathways. The computation work demonstrates that creating spatially organized multi‐enzymes on membranes can be an effective strategy to increase final product synthesis in bioengineering systems. 

Abstract Proteins are inherently dynamic, and their conformational ensembles are functionally important in biology. Large-scale motions may govern protein structure–function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging both experimentally and computationally. In this paper we first introduced an unsupervised deep learning-based model, termed Internal Coordinate Net (ICoN), which learns the physical principles of conformational changes from molecular dynamics (MD) simulation data. Second, we selected interpolating data points in the learned latent space that rapidly identify novel synthetic conformations with sophisticated and large-scale sidechains and backbone arrangements. Third, with the highly dynamic amyloid-β_1-42(Aβ42) monomer, our deep learning model provided a comprehensive sampling of Aβ42’s conformational landscape. Analysis of these synthetic conformations revealed conformational clusters that can be used to rationalize experimental findings. Additionally, the method can identify novel conformations with important interactions in atomistic details that are not included in the training data. New synthetic conformations showed distinct sidechain rearrangements that are probed by our EPR and amino acid substitution studies. This approach is highly transferable and can be used for any available data for training. The work also demonstrated the ability for deep learning to utilize learned natural atomistic motions in protein conformation sampling. 

Abstract Understanding the stress distribution within fiber‐reinforced polymers (FRPs) is critical to extending their operational lifespan. The integration of mechanoresponsive molecular force probes, referred to as mechanophores, presents a potential solution by enabling direct monitoring of stress concentrations. In this study, spiropyran (SP) mechanophores (MPs) are embedded within a polydimethylsiloxane (PDMS) matrix to visualize stress localization during loading within a single fiber‐reinforced framework. The SP mechanophore undergoes a transition from a non‐fluorescent state to an active state (merocyanine) through isomerization in response to mechanical forces. Using a single fiber mounted axially within the matrix, the fundamental failure modes observed in conventional fiber‐reinforced composites are replicated. Samples are strained under uniaxial tensile loading along the fiber direction and the localization of stresses is observed via MP activation. Stresses are concentrated in the matrix near the fiber region that gradually decreases away from the fiber surface. Confocal microscopy is used to visualize mechanophore activation and quantitatively assess fluorescence intensity. Finite element modeling is used to develop a calibration to quantify the stresses based on the observed fluorescence intensity. These outcomes underscore the viability of employing these mechanoresponsive molecules as a potential means to visualize real‐time stress distribution, thereby facilitating the design of high‐performance composites. 

Abstract Force‐responsive molecules that produce fluorescent moieties under stress provide a means for stress‐sensing and material damage assessment. In this work, we report a mechanophore based on Diels‐Alder adductTAD‐Anof 4,4′‐(4,4′‐diphenylmethylene)‐bis‐(1,2,4‐triazoline‐3,5‐dione) and initiator‐substituted anthracene that can undergo retro‐Diels‐Alder (rDA) reaction by pulsed ultrasonication and compressive activation in bulk materials. The influence of having C−N versus C−C bonds at the sites of bond scission is elucidated by comparing the relative mechanical strength ofTAD‐Anto another Diels‐Alder adductMAL‐Anobtained from maleimide and anthracene. The susceptibility to undergo rDa reaction correlates well with bond energy, such that C−N bond containingTAD‐Andegrades faster C−C bond containingMAL‐Anbecause C−N bond is weaker than C−C bond. Specifically, the results from polymer degradation kinetics under pulsed ultrasonication shows that polymer containingTAD‐Anhas a rate constant of 1.59×10⁻⁵ min⁻¹, whileMAL‐An(C−C bond) has a rate constant of 1.40×10⁻⁵ min⁻¹. Incorporation ofTAD‐Anin a crosslinked polymer network demonstrates the feasibility to utilizeTAD‐Anas an alternative force‐responsive probe to visualize mechanical damage where fluorescence can be “turned‐on” due to force‐accelerated retro‐Diels‐Alder reaction.