Biology subjects

Dargis, R.

Publications and source records attributed to Dargis, R..

3 recordsLinked to original sources

bioRxiv2026

Engineered nanosponges mitigate peripheral stress-induced neuroinflammation and restore cognitive function

Systemic inflammation is increasingly recognized as a key driver of neuroinflammation and cognitive dysfunction, particularly in the aging population. Yet, therapeutic interventions that broadly attenuate circulating inflammatory mediators without suppressing host immunity remain limited. Here, we report the development of taurine functionalized hyaluronic acid nanosponges (HA Tau) that blunt systemic inflammatory cascades to protect against downstream neurocognitive impairment. Using molecular docking calculations and experimental validations, we show that taurine functionalization enhances multivalent interactions with diverse cytokines, enabling broad-spectrum sequestration of inflammatory proteins from both murine and human plasma while preserving the intrinsic hypochlorous acid neutralizing ability of taurine. In aged mice undergoing orthopedic surgery, systemic administration of HA Tau nanosponges lowered the levels of circulating inflammatory mediators, preserved blood brain barrier integrity, and attenuated glial cell activation. These effects were accompanied by improved hippocampal neuronal activity and spatial working memory in mice. By dampening peripheral inflammatory surges, the nanosponges limit peripheral-to-central inflammatory signaling without directly targeting the central nervous system. Collectively, these findings demonstrate systemic inflammatory modulation could be an effective strategy for mitigating peripheral insult-induced neuroinflammation and cognitive decline, and position HA Tau nanosponges as a versatile biomaterial platform for treating inflammation-driven disorders.

bioengineering↗

bioRxiv2026

Martini 3 Coarse-Grained Model of DNA for Heterogeneous Molecular Systems

DNA often functions in heterogeneous molecular systems containing proteins, lipids, polymers, and other materials. All-atom molecular dynamics simulations can be used to study DNA in these multicomponent systems, but computational cost limits the accessible system sizes and time scales. Coarse-grained models extend these scales, but existing DNA models are generally not designed for interactions with a broad range of other molecular species. To fill this gap, we develop a coarse-grained model of DNA designed for use with the Martini 3 force field. The model was parameterized through an iterative Bayesian optimization workflow, which used a scaled Wasserstein metric to compare distributions of local geometrical features and global structure from coarse-grained simulations against all-atom reference simulations. The optimized model captures key structural and mechanical properties of single- and double-stranded DNA across varying strand lengths and ionic conditions, while retaining compatibility with the broader Martini 3 ecosystem. This compatibility enables DNA to be integrated with a broad range of molecular systems, as we illustrate through simulations of double-stranded DNA bound to a transcription factor, cholesterol-tagged DNA duplex interacting with a lipid bilayer, a crossover-containing DNA nanostructure, and single-stranded DNA adsorbing onto graphene. Together, these results establish a transferable coarse-grained model of DNA for simulations of heterogeneous biomolecular and engineered systems.

biophysics↗

bioRxiv2025

Regulation of Ordinal DNA Translocation Cycle in Bacteriophage {varphi}29 through Trans-Subunit Interactions

Certain viruses such as tailed bacteriophages and herpes simplex virus package double-stranded DNA into empty procapsids via powerful, ring-shaped molecular motors. High resolution structures and force measurements on the DNA packaging motor of bacteriophage {Phi}29 revealed that its five ATPase subunits coordinate ATP hydrolysis with each other to maintain the proper cyclic sequence of DNA translocation steps about the ring. Here, we explore how the {Phi}29 motor regulates translocation by timing key events, namely ATP binding/hydrolysis and DNA gripping, through trans-subunit interactions. We used subunit dimers bound to DNA as our model system, a minimal system that still captures the conformation and trans-subunit interactions of the full pentametric motor complex. Molecular dynamics simulations of all-ATP and mixed ATP-ADP dimers revealed that the nucleotide occupancy of one subunit strongly affects the ability to hydrolyze ATP in the adjacent subunit by altering the free energy landscape of its catalytic glutamate approaching the gamma phosphate of ATP. Specifically, one ATP-bound subunit donates residues in trans that sterically block the neighboring subunits catalytic glutamate. This steric hindrance is resolved when the first subunit hydrolyzes ATP and is ADP-bound. This obstructive mechanism is supported by functional mutagenesis and appears to be conserved across several {Phi}29 relatives. Mutual information analysis of our simulations revealed intersubunit signaling pathways, via the trans-acting obstructive residues, that allow for sensing and communication between the binding pockets of adjacent subunits. This work shows that the sequential order of DNA translocation events amongst subunits is preserved through novel trans-subunit interactions and pathways.

molecular biology↗