Biology subjects

Panek, D.

Publications and source records attributed to Panek, D..

5 recordsLinked to original sources

bioRxiv2026

Scene perception-memory pairing extends to superior parietal cortex

Visual scene analysis relies on a set of scene-selective regions in posterior cerebral cortex (OPA, PPA, MPA), with a paired memory-responsive counterpart located in anterior (LPMA, VPMA) or overlapping cortex (MPMA). The interaction between these pairs of regions is thought to integrate visual input with mnemonic context. Recently, a fourth scene-perception area in superior parietal cortex (SPA) was identified, with a proposed role in visually-guided navigation. Whether this region also has an anterior paired memory region is currently unknown. Across two independent fMRI datasets (total N=24, 14 females) using static or dynamic stimuli and distinct memory tasks, we show that recalling visual scenes evokes robust responses in a region (referred to here as SPMA) immediately anterior and dorsal to SPA. During resting-state fMRI, SPA preferentially coupled with the other scene-perception areas, while SPMA preferentially coupled with the other place memory areas. At the whole-brain level, seed-based connectivity revealed that SPA sits at the confluence of four processing streams spanning regions implicated in egocentric scene perception, map-based navigation, perspective taking, and goal-directed movement. These findings extend the perception-memory motif associated with visual scene processing to the fourth cortical surface. The widespread anatomical coupling between scene-perception and memory processes reflects the importance of this interaction for flexible, context-grounded navigation.

neuroscience↗

bioRxiv2026

Learning the structural diversity in random protein sequence space

The universe of possible protein sequences is astronomically large, yet our understanding of the sequence-structure relationship is confined to the infinitesimal fraction used currently by life. Determining whether "foldable" architectures are rare singularities or accessible solutions is critical for understanding protein evolution and designing novel proteins. Here, we map the structural landscape of random sequence space by screening one million synthetic proteins using a high-throughput in vivo FRET biosensor. We reveal that this space is structurally heterogeneous, populated not only by disordered chains and stress-inducing aggregates but also by "benign" compact structures that resemble globular proteins and evade cellular chaperone responses. By training machine learning models on these phenotypes, we show that structural potential is learnable and generalizes to natural proteomes. These findings demonstrate that biology-like folds are accessible from random sequences with surprising frequency, providing data required to expand generative protein design beyond evolutionary priors.

synthetic biology↗

bioRxiv2025

Substrate elasticity regulates cytoskeletal remodeling and mechanical behavior of U2OS osteosarcoma cells

Substrate elasticity plays a pivotal role in regulating the morphology, mechanical properties, and cytoskeletal organization of cancer cells. In this study, we examined the response of U2OS osteosarcoma cells to substrates of varying stiffness, with a particular focus on cytoskeletal remodeling, cell elasticity, and microparticle internalization. To simulate environments of moderate and high stiffness, cells were cultured on polyacrylamide (PA) hydrogels with a stiffness of 40 kPa and on rigid glass substrates, respectively. Changes in cell morphology and cytoskeletal organization were assessed using fluorescence microscopy, while cell mechanical properties were measured using atomic force microscopy (AFM). To investigate the relationship between substrate mechanics and endocytic activity, carboxylated fluorescent 2 {micro}m latex microspheres were introduced to the cell culture system. Our study showed that cell spreading increased with substrate stiffness. U2OS cells cultured on glass exhibited a significantly larger surface area, more actin stress fibers, and a more organized, stretched cytoskeletal architecture compared to cells grown on 40 kPa PA gels. AFM measurements further demonstrated that cells on glass were mechanically stiffer than those on PA substrates. Microparticle uptake was also strongly influenced by substrate stiffness. Cells cultured in the 40 kPa PA gels internalized a significantly greater number of fluorescent microspheres. Notably, these cells frequently formed distinct, cup-like structures composed of microtubules around the beads. Three-dimensional image reconstructions revealed that these structures encapsulate the particles in an asymmetrical manner, indicative of active cytoskeletal remodeling. To better understand the molecular composition of these microtubule-based structures, we analyzed the localization of selected microtubule-associated proteins (MAPs), including IQGAP1, CLIP1, and MARK2 (Conboy J.P. et al. 2024). Interestingly, only IQGAP1 was localized prominently to the microtubule cups on 40 kPa gels, often forming ring-like structures surrounding the beads. In some cases, these rings were observed independently of detectable microtubules, suggesting the involvement of an active, possibly microtubule-initiated, endocytic process. In conclusion, our findings demonstrate that substrate stiffness modulates multiple aspects of U2OS cell behavior, including morphology, cytoskeletal arrangement, mechanical properties, and microparticle uptake. These results underscore the mechanosensitive nature of osteosarcoma cells and highlight novel roles for microtubule structures and MAPs, particularly IQGAP1 in stiffness-dependent cellular uptake mechanisms.

biophysics↗

bioRxiv2023

Topical siRNA therapy of diabetic-like wound healing

Non-healing wounds are a serious complication in diabetic patients. One of the detrimental factors contributing to limited wound healing is the accumulation of metalloproteinase-9 (MMP-9) in the wound. Selective inhibition of MMP-9 is one of the established therapeutic targets for diabetic wound healing and is therefore of great interest. Here we focused on development of gene silencing system for localized delivery of antisense siRNA against MMP-9 into the wound. We have developed a functional and biocompatible wound dressing allowing controlled release of a traceable vector loaded with the target siRNA. Specifically, the dressing consists of a degradable scaffold of polymer nanofibers embedded with the vector nanosystem, polymer-coated fluorescent nanodiamonds (FNDs). The biocompatible cationic polymer shell on FNDs was designed and optimized for binding of siRNA and formation of colloidally stable FND-siRNA complexes in physiological environment. A hybrid nanofiber scaffold consisting of poly(vinyl alcohol) and poly(caprolactone) ensured continuous release of FND-siRNA complexes from the dressing. The photostable luminescence of FNDs allowed us to monitor the vector system in the wound. Our dressing was tested on murine fibroblasts and also applied to wounds in a diabetic murine model to evaluate its suitability in terms of in vivo toxicity, biological efficacy and manipulation. The treatment resulted in significant local inhibition of MMP-9 and reduction of the wound healing time. The scar formation for treated diabetic-like animals became comparable with non-treated diabetes-free mice. Our results suggest that the application of our biocompatible dressing loaded with a non-toxic vector nanosystem is an effective and promising approach in gene therapy of non-healing wounds.

bioengineering↗

bioRxiv2022

Phosphorylation of tyrosine 90 in SH3 domain is a new regulatory switch controlling Src kinase

The activation of Src kinase in cells is strictly controlled by intramolecular inhibitory interactions mediated by SH3 and SH2 domains. They impose structural constraints on the kinase domain holding it in a catalytically non-permissive state. The transition between inactive and active conformation is known to be largely regulated by the phosphorylation state of key tyrosines 416 and 527. Here we identified that phosphorylation of tyrosine 90 reduces binding affinity of the SH3 domain to its interacting partners, opens the Src structure, and renders Src catalytically active. This is accompanied by an increased affinity to the plasma membrane, decreased membrane motility and slower diffusion from focal adhesions. Phosphorylation of tyrosine 90 controlling SH3-medited intramolecular inhibitory interaction, analogical to tyrosine 527 regulating SH2-C-terminus bond, enables SH3 and SH2 domains to serve as cooperative but independent regulatory elements. This mechanism allows Src to adopt several distinct conformations of varying catalytic activities and interacting properties, enabling it to operate not as a simple switch but as a tunable regulator functioning as a signaling hub in a variety of cellular processes.

cell biology↗