Lingyun Xiong | Searcharxiv

arXiv2025

A dispersal recolonisation 3D biofilm in vitro model based on co-assembled peptide amphiphiles and clinical wound fluid

Chronic wound infections are sustained by dynamic 3D biofilm cycles involving maturation, dispersal, and recolonisation, yet existing in vitro models fail to reproduce these temporal and structural complexities. Here, we report a strategy that co-assembles a designed protease-inhibitory peptide amphiphile (PA-GF) with patient-derived wound fluid (WF) to reconstruct the complete biofilm life cycle in vitro. The PA-GF sequence incorporates an HWGF motif capable of binding and inhibiting matrix metalloproteinase-9 (MMP-9), thereby preserving the integrity of recolonised biofilms under proteolytic stress. Co-assembling with WF generated a living material that faithfully mimicked the biochemical and mechanical microenvironment of chronic wounds, supporting the formation of stable 3D biofilms capable of dispersal and recolonisation. Furthermore, we established a controllable polymicrobial infection model and validated its translational relevance through antibiotic susceptibility profiling and spatial microbiological analyses. Notably, the antibiotic response patterns of the PA/WF-derived biofilms closely mirrored those observed in a rat wound infection in vivo model. Collectively, our findings demonstrate that co-assembling living materials can recapitulate the nutritional composition, 3D architecture, and recolonisation dynamics of in vivo infectious biofilms, offering a physiologically relevant and customisable platform for investigating chronic wound infections and accelerating anti-biofilm drug discovery.

physics.med-ph↗

arXiv2023

Are physiological oscillations 'physiological'?

Despite widespread and striking examples of physiological oscillations, their functional role is often unclear. Even glycolysis, the paradigm example of oscillatory biochemistry, has seen questions about its oscillatory function. Here, we take a systems approach to summarize evidence that oscillations play critical physiological roles. Oscillatory behavior enables systems to avoid desensitization, to avoid chronically high and therefore toxic levels of chemicals, and to become more resistant to noise. Oscillation also enables complex physiological systems to reconcile incompatible conditions such as oxidation and reduction, by cycling between them, and to synchronize the oscillations of many small units into one large effect. In pancreatic beta cells, glycolytic oscillations are in synchrony with calcium and mitochondrial oscillations to drive pulsatile insulin release, which is pivotal for the liver to regulate blood glucose dynamics. In addition, oscillation can keep biological time, essential for embryonic development in promoting cell diversity and pattern formation. The functional importance of oscillatory processes requires a rethinking of the traditional doctrine of homeostasis, holding that physiological quantities are maintained at constant equilibrium values, a view that has largely failed us in the clinic. A more dynamic approach will enable us to view health and disease through a new light and initiate a paradigm shift in treating diseases, including depression and cancer. This modern synthesis also takes a deeper look into the mechanisms that create, sustain and abolish oscillatory processes, which requires the language of nonlinear dynamics, well beyond the linearization techniques of equilibrium control theory.

q-bio.TO↗