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1.
J Am Chem Soc ; 139(24): 8102-8105, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28598147

RESUMO

This paper describes the supramolecular assembly of a macrocyclic ß-sheet containing residues 16-22 of the ß-amyloid peptide, Aß. X-ray crystallography reveals that the macrocyclic ß-sheet assembles to form double-walled nanotubes, with an inner diameter of 7 nm and outer diameter of 11 nm. The inner wall is composed of an extended network of hydrogen-bonded dimers. The outer wall is composed of a separate extended network of ß-barrel-like tetramers. These large peptide nanotubes pack into a hexagonal lattice that resembles a honeycomb. The complexity and size of the peptide nanotubes rivals some of the largest tubular biomolecular assemblies, such as GroEL and microtubules. These observations demonstrate that small amyloidogenic sequences can be used to build large nanostructures.


Assuntos
Peptídeos beta-Amiloides/química , Compostos Macrocíclicos/química , Nanotubos/química , Fragmentos de Peptídeos/química , Peptídeos/síntese química , Cristalografia por Raios X , Ligação de Hidrogênio , Modelos Moleculares , Estrutura Molecular , Peptídeos/química
2.
Nat Commun ; 14(1): 6341, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37816732

RESUMO

Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors. We find that ablation of neural precursor cells or conditional knockout of VEGF impairs neuronal and vascular reparative responses and worsens recovery. Replacement of VEGF is sufficient to induce neural repair and recovery. We also provide evidence that CXCL12 from peri-infarct vasculature signals to CXCR4-expressing cells arising from the SVZ to direct their ectopic migration. These results support a model in which vasculature surrounding the site of injury attracts cells from the SVZ, and these cells subsequently provide trophic support that drives neural repair and recovery.


Assuntos
Células-Tronco Neurais , Acidente Vascular Cerebral , Camundongos , Animais , Ventrículos Laterais , Células-Tronco Neurais/fisiologia , Fator A de Crescimento do Endotélio Vascular , Neurogênese/fisiologia , Acidente Vascular Cerebral/terapia
3.
Mater Horiz ; 9(1): 164-193, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34549764

RESUMO

Thermoresponsive supramolecular assemblies have been extensively explored in diverse formats, from injectable hydrogels to nanoscale carriers, for a variety of applications including drug delivery, tissue engineering and thermo-controlled catalysis. Understanding the molecular bases behind thermal sensitivity of materials is fundamentally important for the rational design of assemblies with optimal combination of properties and predictable tunability for specific applications. In this review, we summarize the recent advances in this area with a specific focus on the parameters and factors that influence thermoresponsive properties of soft materials. We summarize and analyze the effects of structures and architectures of molecules, hydrophilic and lipophilic balance, concentration, components and external additives upon the thermoresponsiveness of the corresponding molecular assemblies.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Hidrogéis/química , Interações Hidrofóbicas e Hidrofílicas , Temperatura , Engenharia Tecidual
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