Supramolecular assembly of collagen mimetic peptide D-periodic fibrils and nanoassemblies

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

Abstract The collagen triple helix assembles hierarchically into bundled oligomers, solvated networks and fibers. Synthetic peptide assemblies, driven by supramolecular interactions, can form single helices through intrahelical amino acid pairs, but the principles guiding interhelical associations higher-order structures remain unclear. Here, we incorporate cation- π electrostatic charge pairs to probe interactions elucidate mechanisms driving assembly fibrils, nanotubes, nanosheets. Introducing a fibrillating mimetic resulted in D-periodic fibrils with pH-sensitive gelation. Modifying presentation of also enabled characterization another fibril resembling cartilage collagens, featuring inner outer layers. Enhancing promoted antiparallel assembly, leading formation nanotubes packing behavior correlates where parallel favor formation, drive nanotube nanosheet assembly.

Language: Английский

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Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 12, 2025

Tumors often exhibit greater stiffness compared to normal tissues, primarily due increased deposition within the tumor stroma. Collagen, proteoglycans, laminin, and fibronectin are key components of extracellular matrix (ECM), interacting facilitate ECM assembly. Enhanced fiber density cross-linking result in elevated interstitial fluid pressure, subjecting tumors significant physical stress during growth. This mechanical is transduced intracellularly via integrins, Rho signaling pathway, Hippo thereby promoting invasion. Additionally, pressure fosters glycolysis cells, boosting energy production support metastasis. Mechanical cues also regulate macrophage polarization, maintaining an inflammatory microenvironment conducive survival. In summary, signals play a crucial role growth Understanding these their involvement progression essential for advancing our knowledge biology enhancing therapeutic approaches.

Language: Английский

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Marine collagen bio-composites materials: Interactions with small active molecules and their application in food industry

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 142237 - 142237

Published: March 1, 2025

Language: Английский

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Water and Collagen: A Mystery Yet to Unfold

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Collagen is the most abundant protein in human body and plays an essential role determining mechanical properties of tissues. Both as a monomeric fibrous assemblies, collagen interacts with its surrounding molecules, particular water. Interestingly, while it well established that interaction water strongly influences molecular underlying mechanisms remain largely unknown. Here, we review research conducted over past 30 years on interplay between relevance for tissue properties. We discuss water-collagen relevant time- length scales, ranging from vital stabilizing characteristic triple helix structure to negative impact dehydration A better understanding will help unravel effect mutations defective production collagen-related diseases pinpoint key design features required synthesize collagen-based biomimetic tissues tailored

Language: Английский

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Reinforcement of Fibrillar Collagen Hydrogels with Bioorthogonal Covalent Crosslinks

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract Bioorthogonal covalent crosslinking stabilizes collagen type I hydrogels, improving their structural integrity for tissue engineering applications with encapsulated living cells. The chemical modification required crosslinking, however, interferes the fibrillar nature of collagen, leading instead to an amorphous network without fibers. We demonstrate approach perform bioconjugation chemistry on controlled localization such that modified retains its ability self-assemble into a network, while also displaying functional groups bioorthogonal click chemistry. matrix is formed through sequential process, in which first physically assembles fibers and then covalently crosslinked. This preserves fibrous architecture guiding behavior human corneal mesenchymal stromal cells, reinforcing crosslinks, strengthening stability cell-laden hydrogel against cell-induced contraction enzymatic degradation.

Language: Английский

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Dynamic entity formed by protein and its hydration water

Physical Review Research, Journal Year: 2024, Volume and Issue: 6(3)

Published: Sept. 19, 2024

The interaction between protein and water plays a pivotal role in shaping the structure, dynamics, function of biomacromolecules. A comprehensive understanding this intricate interplay necessitates systematic evaluation strength its consequential impact on dynamics proteins across diverse systems. Despite numerous works coupling them, there are still unanswered questions. Here, we combine neutron scattering isotope labeling to probe their hydration variety We consider different structures varying thermostability as well within living cells with distinct growth temperatures. Simultaneous characterization systems was achieved. Moreover, performed sorption isothermal measurements three representative correlate observed energies governing each system. experimental results underscore that manifesting stronger attractive interactions display diffusionlike higher flexibility upon hydration, concomitant reduced mobility water. Significantly, our findings suggest that, fact, it is facilitates transfer from protein, correlating greater slower diffusion. Published by American Physical Society 2024

Language: Английский

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Heterogeneous Structure and Dynamics of Water in a Hydrated Collagen Microfibril

Biomacromolecules, Journal Year: 2024, Volume and Issue: 25(8), P. 4809 - 4818

Published: July 8, 2024

Collagen type I is well-known for its outstanding mechanical properties which it inherits from hierarchical structure. fibrils may be viewed as a heterogeneous material made of protein, macromolecules (such glycosaminoglycans and proteoglycans) water. Water content modulates the these fibrils. Yet, water fine interactions with protein constituent heterofibrils have only received limited attention. Here, we propose to model collagen hydrated structure tropocollagen molecules assembled in microfibril crystal. We perform large-scale all-atom molecular dynamics simulations hydration beyond onset disassembly. found that structural dynamic vary strongly level microfibril. More importantly, spatially within 67 nm D-spacing periodic Alteration dynamical occur first gap region. Overall, identify change role glue lubricant between arises around 100% while begins disassemble 130% content. Our findings are supported by decrease hydrogen bonding, recovery bulk amorphization packing. reveal unprecedented spatial resolution physiological conditions Beyond process self-assembly emergence fibrils, our results also provide new insights into mineralization

Language: Английский

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Bioarchitectural Design of Bioactive Biopolymers: Structure–Function Paradigm for Diabetic Wound Healing

Biomimetics, Journal Year: 2024, Volume and Issue: 9(5), P. 275 - 275

Published: May 4, 2024

Chronic wounds such as diabetic ulcers are a major complication in diabetes caused by hyperglycemia, prolonged inflammation, high oxidative stress, and bacterial bioburden. Bioactive biopolymers have been found to biological response wound tissue microenvironments used for developing advanced engineering strategies enhance healing. These possess innate bioactivity biodegradable, with favourable mechanical properties. However, their is highly dependent on structural properties, which need be carefully considered while healing strategies. Biopolymers alginate, chitosan, hyaluronic acid, collagen previously solutions but the modulation of structural/physico-chemical properties differential not prime focus. Factors molecular weight, degree polymerization, amino acid sequences, hierarchical structures can spectrum immunomodulatory, anti-bacterial, anti-oxidant that could determine fate wound. The current narrative review addresses structure–function relationship bioactive promoting chronic emphasis ulcers. This highlights characterization under research designing biomaterials maximize inherent potency better regeneration outcomes, especially context

Language: Английский

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Is Deuterium Fractionation a Major Controlling Factor in Human Metabolism and Cancer? An Essential Role for Proline

Published: June 19, 2024

Deuterium is a heavy nonradioactive isotope of hydrogen, having neutron as well proton, making it twice heavy. It natural element, present at 156 parts per million in seawater. The ATPase pumps the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage pumps, producing stutter that can cause reactive oxygen release inefficiencies synthesis. Cellular metabolism incorporates several novel mechanisms assure low deuterium content other organelles. Nicotinamide adenine dinucleotide (NAD) major carrier depleted (deupleted) protons supply mitochondria. Many enzymes, especially flavoproteins, are able use tunneling fractionate out deuterium. In this paper, we argue amino acid proline trap sequester deuterium, peptidyl prolyl isomerases (PPIases) play central role facilitating trapping proline-rich proteins, most notably collagen. endothelial glycocalyx also sequesters gelled water lining blood vessels, creating battery promoting circulation. Excess promotes cancer growth, cells large quantities lactate via aerobic glycolysis help reverse overload, systemically.

Language: Английский

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Is Deuterium Fractionation a Major Controlling Factor in Human Metabolism and Cancer? An Essential Role for Proline

Published: June 19, 2024

Deuterium is a heavy nonradioactive isotope of hydrogen, having neutron as well proton, making it twice heavy. It natural element, present at 156 parts per million in seawater. The ATPase pumps the mitochondria utilize proton motive force to drive ATP synthesis, and deuterons damage pumps, producing stutter that can cause reactive oxygen release inefficiencies synthesis. Cellular metabolism incorporates several novel mechanisms assure low deuterium content other organelles. Nicotinamide adenine dinucleotide (NAD) major carrier depleted (deupleted) protons supply mitochondria. Many enzymes, especially flavoproteins, are able use tunneling fractionate out deuterium. In this paper, we argue amino acid proline trap sequester deuterium, peptidyl prolyl isomerases (PPIases) play central role facilitating trapping proline-rich proteins, most notably collagen. endothelial glycocalyx also sequesters gelled water lining blood vessels, creating battery promoting circulation. Excess promotes cancer growth, cells large quantities lactate via aerobic glycolysis help reverse overload, systemically.

Language: Английский

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