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Polymer brushes have witnessed extensive utilization and progress, driven by their distinct attributes in surface modification, tethered group functionality, and tailored interactions at the nanoscale, enabling them for various scientific and industrial applications of coatings, sensors, switchable/responsive materials, nanolithography, and lab-on-a-chips. Despite the wealth of experimental investigations into polymer brushes, this review primarily focuses on computational studies of antifouling polymer brushes with a strong emphasis on achieving a molecular-level understanding and structurally designing antifouling polymer brushes. Computational exploration covers three realms of thermotical models, molecular simulations, and machine-learning approaches to elucidate the intricate relationship between composition, structure, and properties concerning polymer brushes in the context of nanotribology, surface hydration, and packing conformation. Upon acknowledging the challenges currently faced, we extend our perspectives toward future research directions by delineating potential avenues and unexplored territories. Our overarching objective is to advance our foundational comprehension and practical utilization of polymer brushes for antifouling applications, leveraging the synergy between computational methods and materials design to drive innovation in this crucial field. 

Antifreezing hydrogels are essential for materials design and practical applications, but their development and understanding have been challenging due to their high-water content. Current antifreezing hydrogels typically rely on organic solvents or the addition of antifreezing agents. In this study, we present a novel crosslinking strategy to fabricate antifreezing hydrogels without the need for additional antifreezing agents. We introduce a new crosslinker, PEGn-EGINA, which combines highly hydrophilic EGINA with polyethylene glycol (PEG) of varying molecular weights. Utilizing PEGn-EGINA as the crosslinker, we synthesize Agar/Polyacrylamide (Agar/PAAm) double-network hydrogels, alongside conventional MBAA-crosslinked hydrogels for comparison. The resulting PEGn-EGINA-crosslinked hydrogels exhibit inherent antifreezing properties and retain their mechanical integrity even at subzero temperatures for extended periods. Molecular dynamics (MD) simulations further reveal that the antifreezing behavior observed in the PEGn-EGINA-crosslinked hydrogels can be attributed to their highly hydrophilic and tightly crosslinked double-network structures. These structures enable strong bindings between water and the hydrogel network, thus effectively preventing the formation of ice crystals within the hydrogels. Notably, PEGn-EGINA-crosslinked hydrogels not only demonstrate superior mechanical performance compared to MBAA-crosslinked hydrogels, but also maintain their mechanical properties even in frozen conditions, making them suitable for a wide range of applications. This study presents a simple yet effective design concept for highlighting the role of novel crosslinker in enhancing antifreezing and mechanical properties, showcasing their potential for various applications that require both antifreezing capabilities and robust mechanical performance. 

Misfolding and aggregation of amyloid peptides are critical pathological events in numerous protein misfolding diseases (PMDs), such as Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). While developing effective amyloid detectors and inhibitors to probe and prevent amyloid aggregation is a crucial diagnostic and therapeutic strategy for treating debilitating diseases, it is important to recognize that amyloid detection and amyloid prevention are two distinct strategies for developing pharmaceutical drugs. Here, we reported novel fluorescent BO21 as a versatile “dual-function, multi-target” amyloid probe and inhibitor for detecting and preventing amyloid aggregates of different sequences (Aβ, hIAPP, or hCT) and sizes (monomers, oligomers, or fibrils). As an amyloid probe, BO21 demonstrated a higher sensitivity and binding affinity to oligomeric and fibrillar amyloids compared to ThT, resulting in up to 18–39 fold fluorescence enhancements. As an amyloid inhibitor, BO21 also demonstrated its strong amyloid inhibition property by effectively preventing amyloid aggregation, disaggregating preformed amyloid fibrils, and reducing amyloid-induced cytotoxicity. The findings of this study offer a new perspective for the discovery of dual-functional amyloid probes and inhibitors, which have the potential to greatly expand the diagnostic and therapeutic treatments available for PMDs. 

The development and understanding of antifreezing hydrogels are crucial both in principle and practice for the design and delivery of new materials. The current antifreezing mechanisms in hydrogels are almost exclusively derived from their incorporation of antifreezing additives, rather than from the inherent properties of the polymers themselves. Moreover, developing a computational model for the independent yet interconnected double-network (DN) structures in hydrogels has proven to be an exceptionally difficult task. Here, we develop a multiscale simulation platform, integrating ‘random walk reactive polymerization’ (RWRP) with molecular dynamics (MD) simulations, to computationally construct a physically-chemically linked PVA/PHEAA DN hydrogels from monomers that mimic a radical polymerization and to investigate water structures, dynamics, and interactions confined in PVA/PHEAA hydrogels with various water contents and temperatures, aiming to uncover antifreezing mechanism at atomic levels. Collective simulation results indicate that the antifreezing property of PVA/PHEAA hydrogels arises from a combination of intrinsic, strong water-binding networks and crosslinkers and tightly crosslinked and interpenetrating double-network structures, both of which enhance polymer-water interactions for competitively inhibiting ice nucleation and growth. These computational findings provide atomic-level insights into the interplay between polymers and water molecules in hydrogels, which may determine their resistance to freezing.

 

Amyloids and antimicrobial peptides have traditionally been recognized as distinct families with separate biological functions and targets. However, certain amyloids and antimicrobial peptides share structural and functional characteristics that contribute to the development of neurodegenerative diseases. Specifically, the aggregation of amyloid-β (Aβ) and microbial infections are interconnected pathological factors in Alzheimer’s disease (AD). In this study, we propose and demonstrate a novel repurposing strategy for an antimicrobial peptide of protegrin-1 (PG-1), which exhibits the ability to simultaneously prevent Aβ aggregation and microbial infection both in vitro and in vivo. Through a comprehensive analysis using protein, cell, and worm assays, we uncover multiple functions of PG-1 against Aβ, including the following: (i) complete inhibition of Aβ aggregation at a low molar ratio of PG-1/Aβ = 0.25:1, (ii) disassembly of the preformed Aβ fibrils into amorphous aggregates, (iii) reduction of Aβ-induced cytotoxicity in SH-SY5Y cells and transgenic GMC101 nematodes, and (iv) preservation of original antimicrobial activity against P.A., E.coli., S.A., and S.E. strains in the presence of Aβ. Mechanistically, the dual anti-amyloid and anti-bacterial functions of PG-1 primarily arise from its strong binding to distinct Aβ seeds (KD = 1.24–1.90 μM) through conformationally similar β-sheet associations. This work introduces a promising strategy to repurpose antimicrobial peptides as amyloid inhibitors, effectively targeting multiple pathological pathways in AD. 

Since hIAPP (human islet amyloid polypeptide) aggregation and microbial infection are recognized as significant risk factors that contribute to the pathogenesis of type II diabetes (T2D), targeting these catastrophic processes simultaneously may have a greater impact on the prevention and treatment of T2D. Different from the well-studied hIAPP inhibitors, here we propose and demonstrate a repurposing strategy for an antimicrobial peptide, aurein, which can simultaneously modulate hIAPP aggregation and inhibit microbial infection. Collective data from protein, cell, and bacteria assays revealed multiple functions of aurein including (i) promotion of hIAPP aggregation at a low molar ratio of aurein:hIAPP = 0.5 : 1–2 : 1, (ii) reduction of hIAPP-induced cytotoxicity in RIN-m5F cells, and (iii) preservation of original antimicrobial activity against E. coli., S.A., and S.E. strains in the presence of hIAPP. These functions of aurein are mainly derived from its strong binding to different hIAPP seeds through conformationally similar β-sheet association. Our study provides a promising avenue for the repurposing of antimicrobial peptides (such as aurein) as amyloid modulators for blocking at least two pathological pathways in T2D. 

Neurodegenerative diseases and cancers are considered to be two families of diseases caused by completely opposite cell-death mechanisms: the former caused by premature cell death, with the latter due to the increased resistance to cell death. Growing epidemiologic evidence appear to suggest an inverse correlation between neurodegenerative diseases and cancers. However, pathological links, particularly from a protein-cell interaction perspective, between these two families of diseases remains to be proven. Here, a fundamental study investigates the effects of three amyloid proteins of Aβ (associated with AD), hIAPP (associated with T2D), and hCT (associated with MTC) on pancreatic cancer (PANC-1) cells. Collective results demonstrate a general inhibitory activity of all of three amyloid proteins on cancer cell proliferation, but inhibition efficiencies are strongly dependent on amyloid sequence (Aβ, hIAPP, hCT), concentration (IC25, IC50, IC75), and aggregation states (monomers, oligomers). Amyloid proteins exhibit two pathways against cancer cells: amyloid monomer-induced ROS production to inhibit cell growth and amyloid oligomer-induced membrane disruption to kill cells. Collectively, the results demonstrate a general inhibition function of amyloid proteins to induce cancer cell death by preventing cell proliferation, suppressing cell migration, promoting reactive oxygen species production, and disrupting cell membranes. 

Bilayer hydrogels encoded with smart functions have emerged as promising soft materials for engineered biological tissues and human-machine interfaces, due to the versatility and flexibility in designing their mechanical and chemical properties. However, conventional fabrication strategies often require multiple complicated steps to create an anisotropic bilayer structure with poor interfaces, which significantly limit the scope of bilayer hydrogel applications. Here, we reported a general, one-pot, macrophase separation strategy to fabricate a family of bilayer hydrogels made of vinyl and styryl monomers with a seamless interface and a controllable layer separation efficiency (20–99%). The working principle of a macrophase separation strategy allows for the decoupling of the two gelation processes to form distinct vinyl- and styryl-enriched layers by manipulating competitive polymerization reactions between vinyl and styryl monomers. This work presents a straightforward approach and a diverse range of radical monomers, which can be utilized to create next-generation bilayer hydrogels, beyond a few available today.