Biology subjects

Kim, H.-W.

Publications and source records attributed to Kim, H.-W..

8 recordsLinked to original sources

bioRxiv2026

Osmotic Coupling of Mechanics and Epigenetics Regulates Chromatin Phase Organization

Cells experience epigenetic, osmotic, and mechanical perturbations that reorganize chromatin, yet how these distinct cues are integrated into a common physical response of the nucleus remains unclear. Here, we identify nuclear hydration as a central state variable that links microenvironmental perturbations to chromatin phase organization and nuclear mechanics. We develop a non-equilibrium mesoscale model that couples chromatin elasticity, water transport, and epigenetic reaction-diffusion kinetics. In this framework, chromatin behaves as a deformable polymer that segregates into coexisting water-rich euchromatic and water-poor heterochromatic phases, whose compositions and morphologies are regulated by hydration-dependent swelling, elastic strain, and histone-mark interconversion. The model predicts that epigenetic perturbations, osmotic shocks, and volume-changing mechanical loads reorganize chromatin by shifting intranuclear water content, nuclear volume, and euchromatin-heterochromatin phase balance. It further predicts that anisotropic forces impose directional strain, driving heterochromatin elongation, alignment, and lamellar transitions. Quantitative comparisons with super-resolution imaging, AFM and chromatin-accessibility measurement - across pharmacological, osmotic, and mechanical perturbations including confinement and micropatterning - support these predictions. Together, our results establish a chemo-mechano-osmotic framework in which nuclear hydration integrates biochemical and biophysical cues to regulate chromatin organization across scales.

biophysics↗

bioRxiv2026

Ongoing brain state dynamics shape spontaneous awake reactivation and its relationship with memory

Memory reactivation is thought to support memory consolidation, but how ongoing brain states shape awake reactivation and its relationship to memory remain poorly understood. Here, we asked whether spontaneous hippocampal-cortical reactivation during awake rest is embedded in ongoing brain state dynamics by examining its coupling with whole-brain activity patterns and infra-slow global signal (GS) fluctuations, and whether these dynamics shape its relationship to memory retention. Reactivation preferentially occurred during an internally oriented brain state characterized by default mode network activation and dorsal attention network suppression, as well as states that reinstated encoding-related visual activity. Reactivation also clustered around the peak of infra-slow GS fluctuations and in high GS amplitude time windows, features previously associated with lower arousal. Importantly, the relationship between reactivation and memory depended on the ongoing brain state: distinct whole-brain activity patterns expressed during reactivation were associated with opposing memory outcomes, while reactivation during high GS amplitude windows was positively associated with retention. Together, these findings show that awake memory reactivation is embedded in dynamic whole-brain states that may influence its memory outcome, suggesting that recurring brain states may provide favorable windows for awake memory consolidation.

neuroscience↗

bioRxiv2026

A Multicopper Oxidase from Paenibacillus polyethylenelyticus JNU01 Oxidizes Polyethylene

Polyethylene (PE) is a widely used plastic that persists in the environment and resists breakdown via microbial degradation. In this work, we discovered a new bacterium, Paenibacillus polyethylenelyticus JNU01, that grows on a PE-like wax (PELW, 4 kDa) as its sole carbon source, causing chemical modifications to the substrate and releasing small-molecule products. Genomic and transcriptomic analyses identified a multicopper oxidase (PpMmcO) as a key enzyme candidate for this observed activity. PpMmcO caused surface oxidation, increased hydrophilicity, and the release of oxygenated products such as ketones, alkanes, and alkenoic acids. Scanning electron microscopy confirmed surface damage on both PELW and post-use greenhouse PE films. Weight loss analysis showed mass losses of 5.2% for the PELW powder and 1.6% for the greenhouse PE film after treatment with wild-type PpMmcO. We propose a radical-mediated pathway catalyzed by PpMmcO. These findings identify a new bacterium and enzyme capable of initiating PE oxidation and provide insight into biological processes that may act on polyethylene.

microbiology↗

bioRxiv2025

The protein phosphatase 2C domain contributes to the pathobiological function of adenylyl cyclase in Cryptococcus neoformans

Adenylyl cyclase produces cyclic adenosine monophosphate, a signalling molecule that controls fungal development and virulence. Fungal adenylyl cyclases are distinguished by the presence of a conserved protein phosphatase 2C domain, whose function remains unknown. Here we show that the protein phosphatase 2C domain of Cac1, the adenylyl cyclase of the human pathogen Cryptococcus neoformans, has an unusual structure but functions as a metal-dependent serine/threonine phosphatase. Deletion of this domain or the adenylyl cyclase catalytic domain demonstrated that the protein phosphatase 2C domain is required for full Cac1 activity, influencing melanin and capsule synthesis, sexual differentiation, titan cell formation, and cell wall integrity. Notably, loss of the protein phosphatase 2C domain induces type 2 helper T-cell-biased immunity and extensive pulmonary damage yet does not cause mortality in mice. Integrated transcriptomic and phosphoproteomic analyses further revealed shared and domain-specific signalling outputs. Together, these findings define a pivotal role for the adenylyl cyclase-linked protein phosphatase 2C domain in C. neoformans pathobiology.

microbiology↗

bioRxiv2024

Bioprinting of aptamer-based programmable bioinks to modulate multiscale microvascular morphogenesis in 4D

Dynamic growth factor presentation influences how individual endothelial cells assemble into complex vascular networks. Here, we developed programmable bioinks that facilitate dynamic VEGF presentation to guide vascular morphogenesis within 3D-bioprinted constructs. We leveraged aptamers high affinity for rapid VEGF sequestration in spatially confined regions and utilized aptamer-complementary sequence (CS) hybridization to tune VEGF release kinetics temporally, days after bioprinting. We show that spatial resolution of programmable bioink, combined with CS-triggered VEGF release, significantly influences alignment, organization, and morphogenesis of microvascular networks in bioprinted constructs. The presence of aptamer-tethered VEGF and the generation of instantaneous VEGF gradients upon CS-triggering restricted hierarchical network formation to the printed aptamer regions at all spatial resolutions. Network properties improved as the spatial resolution decreased, with low-resolution designs yielding the highest network properties. Specifically, CS-treated low-resolution designs exhibited significant vascular network remodeling, with increase in vessel density(1.35-fold), branching density(1.54-fold), and average vessel length(2.19-fold) compared to non-treated samples. Our results suggests that CS acts as an external trigger capable of inducing time-controlled changes in network organization and alignment on-demand within spatially localized regions of a bioprinted construct. We envision that these programmable bioinks will open new opportunities for bioengineering functional, hierarchically self-organized vascular networks within engineered tissues.

bioengineering↗

bioRxiv2024

Nanofibrous Wound Dressing with a Smart Drug Delivery System: Poly(N-Isopropylacrylamide)-Conjugated Polycaprolactone Nanofibers Loaded with Curcumin

In response to clinical demands for advanced wound dressings, a "smart bandage" was developed by combining polycaprolactone (PCL) nanofibers and the thermoresponsive polymer poly(N-isopropylacrylamide) (PNIPAAm). This bandage incorporates curcumin, an anti-inflammatory and antioxidant agent, to enhance wound healing. The LCST of PNIPAAm (32{degrees}C) enables an "on-off" drug delivery system, transitioning from a hydrophilic coil to a hydrophobic state. The nanofiber matrix was characterized using FTIR spectroscopy, SEM, water contact angle, and dynamic mechanical analysis. Curcumin release was assessed both above and below the LCST. The bandage is comfortable, easy to apply and remove, and promotes rapid wound healing. In vitro studies confirmed its non-toxicity to human dermal fibroblast cells. This "smart bandage" represents a significant advancement in wound care, with the potential to meet clinical requirements and enhance patient compliance, offering controlled drug delivery combined with the therapeutic benefits of curcumin.

bioengineering↗

bioRxiv2024

Matrix-rigidity cooperates with biochemical cues in M2 macrophage activation through increased nuclear deformation and chromatin accessibility

Macrophages encounter a myriad of biochemical and mechanical stimuli across various tissues and pathological contexts. Notably, matrix rigidity has emerged as a pivotal regulator of macrophage activation through mechanotransduction. However, the precise mechanisms underlying the interplay between mechanical and biochemical cues within the nuclear milieu remain elusive. Here we elucidate how the increased matrix rigidity drives macrophages to amplify alternatively-activated (M2 phenotype) signalings cooperatively with biochemical cues (e.g., IL4/13) through altered nuclear mechanics. Notably, we found that reconstructed podosome-like F-actins and contractility induced nucleus deformation, opening nuclear pores, which facilitates nuclear translocation of the key transcription factor STAT6. Furthermore, the altered nuclear mechanics increased chromatin accessibility induced by H3K9 methylation, particularly of M2-associated gene promoters. These cooperative events of the mechano-chemical signaling at the cytoskeletal-to-nuclear domains facilitated M2 transcriptional activation and cellular functions. We further evidenced the rigidity-primed M2 macrophages were immunosuppressive and accumulated in stiffened tumor tissues. This study proposes a mechanism by which matrix mechanics crosstalks with biochemical signals to potentiate macrophage activation through nuclear mechanosensing and chromatin modifications, offering insights into macrophage mechanobiology and its therapeutic modulations.

bioengineering↗

bioRxiv2021

Chronic opioid treatment arrests neurodevelopment and alters synaptic activity in human midbrain organoids

The impact of long-term opioid exposure on the embryonic brain is crucial to healthcare due to the surging number of pregnant mothers with an opioid dependency. Current studies on the neuronal effects are limited due to human brain inaccessibility and cross-species differences among animal models. Here, we report a model to assess cell-type specific responses to acute and chronic fentanyl treatment, as well as fentanyl withdrawal, using human induced pluripotent stem cell (hiPSC)-derived midbrain organoids. Single cell mRNA sequencing (25,510 single cells in total) results suggest that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters the pathways associated with synaptic activities and neuron projection. Acute fentanyl treatment, however, increases dopamine release but does not induce significant changes in gene expressions of cell lineage development. To date, our study is the first unbiased examination of midbrain transcriptomics with synthetic opioid treatment at the single cell level.

neuroscience↗