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2.
Mol Cell ; 70(1): 106-119.e10, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29625032

RESUMO

A current challenge in cell motility studies is to understand the molecular and physical mechanisms that govern chemokine receptor nanoscale organization at the cell membrane, and their influence on cell response. Using single-particle tracking and super-resolution microscopy, we found that the chemokine receptor CXCR4 forms basal nanoclusters in resting T cells, whose extent, dynamics, and signaling strength are modulated by the orchestrated action of the actin cytoskeleton, the co-receptor CD4, and its ligand CXCL12. We identified three CXCR4 structural residues that are crucial for nanoclustering and generated an oligomerization-defective mutant that dimerized but did not form nanoclusters in response to CXCL12, which severely impaired signaling. Overall, our data provide new insights to the field of chemokine biology by showing that receptor dimerization in the absence of nanoclustering is unable to fully support CXCL12-mediated responses, including signaling and cell function in vivo.


Assuntos
Citoesqueleto de Actina/metabolismo , Membrana Celular/metabolismo , Movimento Celular , Nanopartículas , Receptores CXCR4/metabolismo , Linfócitos T/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/imunologia , Motivos de Aminoácidos , Animais , Antígenos CD4/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/imunologia , Quimiocina CXCL12/farmacologia , Células HEK293 , Humanos , Células Jurkat , Ligantes , Camundongos Endogâmicos C57BL , Mutação , Multimerização Proteica , Transporte Proteico , Receptores CXCR4/efeitos dos fármacos , Receptores CXCR4/genética , Receptores CXCR4/imunologia , Transdução de Sinais , Imagem Individual de Molécula , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
3.
Nanoscale ; 9(19): 6237-6245, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28338700

RESUMO

The development of piezoelectric layered materials may be one of the key elements enabling expansion of nanotechnology, as they offer a solution for the construction of efficient transducers for a wide range of applications, including self-powered devices. Here, we investigate the piezoelectric effect in multilayer (ML) stepped MoS2 flakes obtained by liquid-phase exfoliation, which is especially interesting because it may allow the scalable fabrication of electronic devices using large area deposition techniques (e.g. solution casting, spray coating, inkjet printing). By using a conductive atomic force microscope we map the piezoelectricity of the MoS2 flakes at the nanoscale. Our experiments demonstrate the presence of electrical current densities above 100 A cm-2 when the flakes are strained in the absence of bias, and the current increases proportional to the bias. Simultaneously collected topographic and current maps demonstrate that the edges of stepped ML MoS2 flakes promote the piezoelectric effect, where the largest currents are observed. Density functional theory calculations are consistent with the ring-like piezoelectric potential generated when the flakes are strained, as well as the enhanced piezoelectric effect at edges. Our results pave the way to the design of piezoelectric devices using layered materials.

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