bioRxiv - Biophysics最新文献_第6页

Membrane-assisted Aβ40 aggregation pathways 膜辅助 Aβ40 聚合途径

bioRxiv - Biophysics Pub Date : 2024-09-08 DOI: 10.1101/2024.09.05.611426

Fidha Nazreen Kunnath Muhammedkutty, Huan-Xiang Zhou

引用次数: 0

Modelling how lamellipodia-driven cells maintain persistent migration and interact with external barriers 模拟叶状薄片驱动的细胞如何保持持续迁移并与外部障碍相互作用

bioRxiv - Biophysics Pub Date : 2024-09-07 DOI: 10.1101/2024.09.06.611667

Shubhadeep Sadhukhan, Cristina Martinez-Torres, Samo Penic, Carsten Beta, Ales Iglic, Nir S. gov

{"title":"Modelling how lamellipodia-driven cells maintain persistent migration and interact with external barriers","authors":"Shubhadeep Sadhukhan, Cristina Martinez-Torres, Samo Penic, Carsten Beta, Ales Iglic, Nir S. gov","doi":"10.1101/2024.09.06.611667","DOIUrl":"https://doi.org/10.1101/2024.09.06.611667","url":null,"abstract":"Cell motility is fundamental to many biological processes, and cells exhibit a variety of migration patterns. Many motile cell types follow a universal law that connects their speed and persistency, a property that can originate from the intracellular transport of polarity cues due to the global actin retrograde flow. This mechanism was termed the ``Universal Coupling between cell Speed and Persistency\"(UCSP). Here we implemented a simplified version of the UCSP mechanism in a coarse-grained ``minimal-cell\" model, which is composed of a three-dimensional vesicle that contains curved active proteins. This model spontaneously forms a lamellipodia-like motile cell shape, which is however sensitive and can depolarize into a non-motile form due to random fluctuations or when interacting with external obstacles. The UCSP implementation introduces long-range inhibition, which stabilizes the motile phenotype. This allows our model to describe the robust polarity observed in cells and explain a large variety of cellular dynamics, such as the relation between cell speed and aspect ratio, cell-barrier scattering, and cellular oscillations in different types of geometric confinements.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142178255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nonequilibrium phases of a biomolecular condensate facilitated by enzyme activity 酶活性促进生物分子凝聚物的非平衡相

bioRxiv - Biophysics Pub Date : 2024-08-11 DOI: 10.1101/2024.08.11.607499

Sebastian T Coupe, Nikta Fakhri

{"title":"Nonequilibrium phases of a biomolecular condensate facilitated by enzyme activity","authors":"Sebastian T Coupe, Nikta Fakhri","doi":"10.1101/2024.08.11.607499","DOIUrl":"https://doi.org/10.1101/2024.08.11.607499","url":null,"abstract":"Biomolecular condensates represent a frontier in cellular organization, existing as dynamic materials driven out of equilibrium by active cellular processes. Here we explore active mechanisms of condensate regulation by examining the interplay between DEAD-box helicase activity and RNA base-pairing interactions within ribonucleoprotein condensates. We demonstrate how the ATP-dependent activity of DEAD-box helicases—a key class of enzymes in condensate regulation—acts as a nonequilibrium driver of condensate properties through the continuous remodeling of RNA interactions. By combining the LAF-1 DEAD-box helicase with a designer RNA hairpin concatemer, we unveil a complex landscape of dynamic behaviors, including time-dependent alterations in RNA partitioning, evolving condensate morphologies, and shifting condensate dynamics. Importantly, we reveal an antagonistic relationship between RNA secondary structure and helicase activity which promotes condensate homogeneity via a nonequilibrium steady state. By elucidating these nonequilibrium mechanisms, we gain a deeper understanding of cellular organization and expand the potential for active synthetic condensate systems.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Faster amylin aggregation on fibrillar collagen hastens diabetic progression through β cell death and loss of function 淀粉样蛋白在纤维胶原上的快速聚集会导致β细胞死亡和功能丧失，从而加速糖尿病的进程

bioRxiv - Biophysics Pub Date : 2024-08-11 DOI: 10.1101/2024.08.10.607320

Md Asrafuddoza Hazari, Gautam Kannan, Akash Kumar Jha, Musale Krushna Pavan, Subrata Dasgupta, Farhin Sultana, Soumya Ranjan Pujahari, Simran Singh, Sarbajeet Dutta, Sai Prasad Pydi, Sankhadeep Dutta, Prasenjit Bhaumik, Hamim Zafar, Ashutosh Kumar, Shamik Sen

{"title":"Faster amylin aggregation on fibrillar collagen hastens diabetic progression through β cell death and loss of function","authors":"Md Asrafuddoza Hazari, Gautam Kannan, Akash Kumar Jha, Musale Krushna Pavan, Subrata Dasgupta, Farhin Sultana, Soumya Ranjan Pujahari, Simran Singh, Sarbajeet Dutta, Sai Prasad Pydi, Sankhadeep Dutta, Prasenjit Bhaumik, Hamim Zafar, Ashutosh Kumar, Shamik Sen","doi":"10.1101/2024.08.10.607320","DOIUrl":"https://doi.org/10.1101/2024.08.10.607320","url":null,"abstract":"Amyloid deposition of the neuroendocrine peptide amylin in islet tissues is a hallmark of type 2 diabetes (T2DM), leading to beta cell toxicity through nutrient deprivation, membrane rupture and apoptosis. Though accumulation of toxic amylin aggregates in islet matrices is well documented, the role of the islet extracellular matrix in mediating amylin aggregation and its pathological consequences remains elusive. Here, we address this question by probing amylin interaction with collagen I (Col I) whose expression in the islet tissue increases during diabetes progression. By combining multiple biophysical techniques, we show that hydrophobic, hydrophilic & cation-pi interactions regulate amylin binding to Col I, with fibrillar collagen driving faster amylin aggregation. Amylin-entangled Col I matrices containing high amounts of amylin induce death and loss of function of INS1E beta-cells. Together, our results illustrate how amylin incorporation in islet matrices through amylin-Col interactions drives T2DM progression by impacting beta-cell viability and insulin secretion.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative comparison of the structural differences between NRAS and its mutations by well-tempered metadynamics simulations 通过温差元动力学模拟定量比较 NRAS 及其突变体之间的结构差异

bioRxiv - Biophysics Pub Date : 2024-08-10 DOI: 10.1101/2024.08.09.607354

Zheyao Hu, Jordi Marti

引用次数: 0

Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level 在单分子水平上观察到哺乳动物朊病毒蛋白的不同折叠机制与不同的疾病易感性

bioRxiv - Biophysics Pub Date : 2024-08-10 DOI: 10.1101/2024.08.09.607387

Uttam Anand, Shubhadeep Patra, Rohith Vedhthaanth Sekar, Craig R Garen, Michael T Woodside

{"title":"Different folding mechanisms in prion proteins from mammals with different disease susceptibility observed at the single-molecule level","authors":"Uttam Anand, Shubhadeep Patra, Rohith Vedhthaanth Sekar, Craig R Garen, Michael T Woodside","doi":"10.1101/2024.08.09.607387","DOIUrl":"https://doi.org/10.1101/2024.08.09.607387","url":null,"abstract":"Misfolding of the protein PrP causes prion diseases in mammals. Disease susceptibility varies widely among species, despite PrP sequences differing by only a few amino acids. How these differences alter PrP folding and misfolding remains unclear. We compared the folding dynamics of single PrP molecules from three species with different disease susceptibility: dogs (immune), hamsters (susceptible), and bank voles (extremely susceptible). Measurements with optical tweezers revealed important differences between the folding cooperativity, pathways, energy barriers, and kinetics of these proteins. In contrast to the two-state folding of hamster PrP, dog PrP always folded through multiple intermediates. However, both featured rapid native folding, homogeneous energy barriers, and no readily observable misfolding. Bank vole PrP also folded via intermediates, but more slowly and via inhomogeneous barriers. Most notably, it formed several metastable misfolded states starting from the unfolded state. Analyzing the sequence of intermediates seen in pulling curves, we found significant differences in the folding pathways for dog and bank vole PrP, implying that sequence mutations altered energy barriers so as to redirect folding pathways. These results show that subtle differences in PrP sequence between species produce profound changes in folding behavior, providing insight into the factors underlying misfolding propensity.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterogenous organization in condensates of multiple transcription factors in embryonic stem cells 胚胎干细胞中多种转录因子凝聚体的异质组织

bioRxiv - Biophysics Pub Date : 2024-08-10 DOI: 10.1101/2024.06.14.599027

Azuki Mizutani, Cheng Tan, Yuji Sugita, Shoji Takada

引用次数: 0

Auditory Cellular Cooperativity Probed Via Spontaneous Otoacoustic Emissions 通过自发声发射探测听觉细胞的合作性

bioRxiv - Biophysics Pub Date : 2024-08-10 DOI: 10.1101/2024.08.09.607375

Christopher Bergevin, Rebecca Whiley, Hero Wit, Geoffrey Manley, Pim van Dijk

{"title":"Auditory Cellular Cooperativity Probed Via Spontaneous Otoacoustic Emissions","authors":"Christopher Bergevin, Rebecca Whiley, Hero Wit, Geoffrey Manley, Pim van Dijk","doi":"10.1101/2024.08.09.607375","DOIUrl":"https://doi.org/10.1101/2024.08.09.607375","url":null,"abstract":"As a sound pressure detector that uses energy to boost both its sensitivity and selectivity, the inner ear is an active non-equilibrium system. The collective processes of the inner ear giving rise to this exquisite functionality remain poorly understood. One manifestation of the active ear across the animal kingdom is the presence of spontaneous otoacoustic emission (SOAE), idiosyncratic arrays of spectral peaks that can be measured using a sensitive microphone in the ear canal.1 Current SOAE models attempt to explain how multiple peaks arise, and generally assume a spatially-distributed tonotopic system. However, the nature of the generators, their coupling, and the role of noise (e.g., Brownian motion) are hotly debated, especially given the inner ear morphological diversity across vertebrates. One means of probing these facets of emission generation is studying fluctuations in SOAE peak properties, which produce amplitude (AM) and frequency modulations (FM). These properties are likely related to the presence of noise affecting active cellular generation elements, and the coupling between generators. To better biophysically constrain models, this study characterizes the fluctuations in filtered SOAE peak waveforms, focusing on interrelations within and across peaks. A systematic approach is taken, examining three species that exhibit disparate inner ear morphologies: humans, barn owls, and green anole lizards. To varying degrees across all three groups, SOAE peaks have intra- (IrP) and interpeak (IPP) correlations indicative of interactions between generative elements. Activity from anole lizards, whose auditory sensory organ is relatively much smaller than that of humans or barn owls, showed a much higher incidence of IPP correlations. Taken together, we propose that these data are indicative of SOAE cellular generators acting cooperatively, allowing the ear to function as an optimized detector.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants 分子动力学模拟揭示了序列上下文在植物基于 ELF3-PrD 的温度感应机制中的作用

bioRxiv - Biophysics Pub Date : 2024-08-10 DOI: 10.1101/2024.08.09.607385

Richard J Lindsay, Rafael Giordano Viegas, VITOR B P LEITE, Philip Anthony Wigge, Sonya M Hanson

{"title":"Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants","authors":"Richard J Lindsay, Rafael Giordano Viegas, VITOR B P LEITE, Philip Anthony Wigge, Sonya M Hanson","doi":"10.1101/2024.08.09.607385","DOIUrl":"https://doi.org/10.1101/2024.08.09.607385","url":null,"abstract":"The evening complex (EC) is a tripartite DNA repressor and a core component of the circadian clock that provides a mechanism for temperature-responsive growth and development of many plants. ELF3, a component of the EC, is a disordered scaffolding protein that blocks transcription of growth genes at low temperature. At increased temperature EC DNA binding is disrupted and ELF3 is sequestered in a reversible nuclear condensate, allowing transcription and growth to proceed. The condensation is driven by a low complexity prion-like domain (PrD), and the sensitivity of the temperature response is modulated by the length of a variable polyQ tract, with a longer polyQ tract corresponding to enhanced condensate formation and hypocotyl growth at increased temperature. Here, a series of computational studies provides evidence that polyQ tracts promote formation of temperature-sensitive helices in flanking residues with potential impacts for EC stability under increasing temperature. REST2 simulations uncover a heat-induced population of condensation-prone conformations that results from the exposure of 'sticky' aromatic residues by temperature-responsive breaking of long-range contacts. Coarse-grained Martini simulations reveal both polyQ tract length and sequence context modulate the temperature dependence of cluster formation. Understanding the molecular mechanism underlying the ELF3-PrD temperature response in plants has implications for technologies including modular temperature-response elements for heat-responsive protein design and agricultural advances to enable optimization of crop yields and allow plants to thrive in increasingly inhospitable environments.","PeriodicalId":501048,"journal":{"name":"bioRxiv - Biophysics","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141945063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generating Multi-state Conformations of P-type ATPases with a Diffusion Model 用扩散模型生成 P 型 ATP 酶的多态构象

bioRxiv - Biophysics Pub Date : 2024-08-09 DOI: 10.1101/2024.08.07.607107

Jingtian Xu, Yong Wang

引用次数: 0