Biology subjects

Adler-Abramovich, L.

Publications and source records attributed to Adler-Abramovich, L..

8 recordsLinked to original sources

bioRxiv2026

A Conserved Mechanism for Positioning Ferredoxin NADP+ Reductase at Photosystem I in Green Algae

The association of ferredoxin-NADP+ reductase (FNR) with thylakoid membranes constitutes a central regulatory node in photosynthetic electron transport, governing NADPH production essential for carbon fixation. In cyanobacteria and higher plants, this interaction is mediated by an intrinsic FNR domain or specialized proteins, yet the mode of recruitment in green algae has remained enigmatic. Here, we show that in the green microalga Chlamydomonas reinhardtii, FNR is directly tethered to photosystem I-LHCI (PSI-LHCI) through a conserved N-terminal -helix of the antenna protein Lhca4. Cryogenic electron microscopy localizes FNR to the stromal side of PSI proximal to Lhca4, while AlphaFold modeling identifies a specific interaction interface, which we validate using isothermal titration calorimetry. Structural modeling further reveals that the spatial separation between PSI-bound FNR and ferredoxin (Fd) is incompatible with direct electron transfer, indicating that it occurs sequentially rather than through a stable PSI-Fd-FNR complex. Comparative analysis demonstrates that the FNR-binding N-terminal motif of Lhca proteins is conserved across diverse green microalgae, suggesting an evolutionarily conserved strategy for positioning FNR at PSI. Collectively, our results uncover a novel mechanism for FNR recruitment and establish a new principle by which photosynthetic electron partitioning is regulated through spatial organization of electron transfer components.

plant biology↗

bioRxiv2026

Neurofilament Light Disordered Tail Mutations Reshape Its Self-Assembled Network Structure

Proteins with intrinsically disordered regions (IDRs) perform essential cellular functions despite lacking stable structures, challenging the traditional structure-function paradigm. Neurofilament-light (NFL) proteins assemble into bottlebrush filaments, whose disordered tail domains mediate nematic hydrogel formation critical for neuronal integrity. Mutations in NFL are linked to Charcot-Marie-Tooth (CMT) disease, yet their molecular effects remain unclear. Here, aiming to gain insight into these molecular mechanisms, we combine small-angle X-ray scattering, microscopy, and deep-learning conformational analysis to investigate CMT-associated NFL tail mutations. We find that these mutations induce pathological hydrogel compaction, disrupt filament nematic order by generating microdomains, and alter water retention dynamics by reshaping of sequence-dependent conformational ensembles, leading to macroscopic network rearrangements. These findings provide mechanistic insight into how subtle sequence changes in IDRs modulate protein network organization and function, informing an understanding of IDR-related pathologies and mutation-based disease characterization.

biophysics↗

bioRxiv2025

3D-Printed Titanium Implants with Bioactive Peptide-polysaccharide Scaffolds for Personalized Bone Reconstruction

Large bone defects caused by trauma, tumor resection, or congenital abnormalities remain a major clinical challenge. Standard titanium implants are widely used due to their strength and biocompatibility, but their bioinert surfaces often lead to poor osseointegration. The emergence of 3D printing has enabled patient-specific titanium implants with tailored architecture and mechanical properties. However, these constructs still lack the bioactivity required for robust and spatially uniform bone integration, particularly within the implant core. To address this limitation, we developed a bioactive, cell-free strategy that integrates porous titanium implants with a nanofibrillar peptide-hyaluronic acid scaffold, delivered either as a hydrogel or in lyophilized form. The scaffold exhibited enhanced enzymatic stability and supported osteoblast-like cell adhesion in vitro. In a rabbit calvarial critical-size bone defect model, scaffold-integrated implants significantly outperformed inert controls, with hydrogel integration nearly doubling inner bone volume and improving trabecular architecture. Histological analysis confirmed enhanced bone-implant integration, active periosteum, healthy marrow, and reduced inflammation. This acellular, growth-factor-free approach combines the structural precision of titanium with the regenerative potential of ECM-mimicking scaffolds, offering a translatable pathway for personalized skeletal repair.

bioengineering↗

bioRxiv2025

A Bioelectronic Scaffold for Label-Free, Real-Time Monitoring of Wound Healing

Chronic wounds and severe burns pose a major clinical challenge, as they often heal slowly or fail to respond to conventional treatments. In addition, there is a critical lack of tools for personalized, continuous monitoring of the healing process. Although progress has been made in both regenerative biomaterials and wearable biosensors, their integration into a unified platform that enables in situ, real-time monitoring of wound healing remains a major challenge. Here, we present a multifunctional bioelectronic scaffold that combines regenerative capability with real-time sensing of cellular activity. The scaffold was fabricated by electrospinning polycaprolactone (PCL) functionalized with the bioactive, self-assembling peptide fluorenylmethoxycarbonyl-phenylalanine-arginine-glycine-aspartic acid (Fmoc-FRGD) to promote cell adhesion and proliferation. For electrical sensing, biocompatible MXene (Ti3C2TX) electrodes were conformally deposited onto the nanofibrous matrix, preserving its biological functionality. This system enables label-free, real-time monitoring of cell viability and coverage using electrical impedance spectroscopy (EIS), offering continuous and quantitative insight into cellular adhesion and proliferation. Extracted impedance parameters at low frequencies exhibit a strong correlation with both cell viability and coverage, providing a non-destructive indicator of wound closure and healing dynamics. This platform offers a promising strategy for advanced wound care, integrating real-time monitoring with biologically supportive materials.

bioengineering↗

bioRxiv2025

Potent Neutralization by Antibodies Targeting the Mpox A28 Protein

Mpox is the most pathogenic Poxvirus in circulation. While several antigens have been identified as targets for neutralizing antibodies, many proteins remain unexplored. We isolated and characterized four monoclonal antibodies (mAbs) targeting the Mpox A28 (OPG153), a virulence factor present on mature Mpox virions. The antibodies were isolated from convalescent individuals, alongside 14 additional mAbs targeting the A35 and H3 proteins. Anti-A28 mAbs potently neutralized Mpox and Vaccinia virus (VACV) through complement-dependent mechanisms involving C1q and C3 deposition. High resolution crystal structures of Anti-A28 mAbs 10M2146 and 8M2110 in complex with VACV A26 revealed two proximal epitopes within the N-terminal domain. Passive transfer of 8M2110 attenuated disease in infected mice. Moreover, immunization with A28 elicited antigen-specific B cells and robust neutralizing antibody responses and provided complete protection against lethal VACV challenge. These findings support Mpox A28 as a promising target for the induction of neutralizing antibodies and antiviral interventions.

immunology↗

bioRxiv2025

Stable, Easy-to-Handle, Fully Autologous Electrospun Polymer-Peptide Skin Equivalent for Severe Burn Injuries

Severe burn injuries represent a significant clinical challenge due to their complex healing process and the high risk of complications, including infection, scarring, and contracture formation. Current therapeutic approaches for burn wound treatment include autologous donor-site grafting and advanced cell therapy techniques like cultured epidermal autografts (CEA), which successfully facilitate wound closure through re-epithelialization. However, CEAs are limited by fragility, shrinkage, lack of a dermal layer, and risks of contamination. Here, aiming to overcome these limitations, we developed a personalized skin equivalent featuring an engineered scaffold composed of electrospun polycaprolactone (PCL) functionalized with the bioactive peptide fluorenylmethyloxycarbonyl-phenylalanine-arginine-glycine-aspartic acid (Fmoc-FRGD). This scaffold is designed to mimic the natural extracellular matrix (ECM), promoting cellular adhesion, integration, and proliferation while maintaining structural integrity. In-vitro analysis demonstrated the scaffolds ability to support multi-layered human skin cell growth, while in-vivo experiments confirmed its efficacy in facilitating wound closure and full-thickness skin regeneration in a murine model. This bioengineered skin equivalent is mechanically robust, easy to handle, fully autologous and exhibits no contraction, offering a transformative therapeutic alternative for the treatment of severe burn injuries.

bioengineering↗

bioRxiv2024

Enhancing Collagen Biosynthesis in Mammalian Cells Through Hypoxia-Mimetic Prolyl Hydroxylase Inhibition

Collagen, the most abundant protein in the extracellular matrix of mammalian cells, is extensively needed in various biotechnological and therapeutic applications, such as tissue engineering and regeneration, cosmetics, and cultivated meat. Despite the increasing demand for natural collagen from non-animal sources, it is mainly produced from animal connective tissues. Recent research has highlighted that under hypoxia, the activation of the hypoxia-inducible factor (HIF) leads to enhanced collagen type I biosynthesis. However, under normal oxygen conditions, HIF activity is downregulated by the HIF-prolyl hydroxylase (PHD) enzyme. We, therefore, hypothesized that inhibiting PHD could elevate HIF transcriptional activity and enhance collagen biosynthesis under normoxia. Our study demonstrates that inhibiting PHD using exogenous small molecules boosts HIF activity and upregulates the key enzymes, collagen prolyl 4-hydroxylases and lysyl hydroxylases, resulting in up to 29-fold increase in collagen type I in embryonic mouse fibroblast NIH/3T3 cells. These findings suggest that targeting PHD can effectively enhance collagen production in mammalian cells. Therefore, modulating key protein signaling pathways presents a promising strategy for enhancing the production of high-yield natural collagen.

cell biology↗

bioRxiv2022

Saliva metabolome alterations after acute stress

Major stress has systemic effects on the body that can have adverse consequences for physical and mental health. However, the molecular basis of these damaging effects remains incompletely understood. Here we use a longitudinal approach to characterise the acute systemic impact of major psychological stress in a pig model. We perform untargeted metabolomics on non-invasively-obtained saliva samples from pigs before and 24-hours after transfer to the novel physical and social environment of a slaughterhouse. The main molecular changes occurring include decreases in amino acids, B-vitamins, and amino acid-derived metabolites synthesized in B-vitamin-dependent reactions, as well as yet-unidentified metabolite features. Decreased levels of several of the identified metabolites are implicated in the pathology of human psychological disorders and neurodegenerative disease, suggesting a possible neuroprotective function. Our results provide a fingerprint of the acute effect of psychological stress on the metabolome and suggest candidate biomarkers with potential roles in stress-related disorders. One Sentence SummaryIdentification of metabolites decreased under acute psychological stress may lead to future discoveries for the prevention and treatment of stress-related disorders.

molecular biology↗