scholarly journals Frontispiz: A Multivariate‐Gated DNA Nanodevice for Spatioselective Imaging of Pro‐metastatic Targets in Extracellular Microenvironment

2022 ◽  
Vol 134 (4) ◽  
Zhichu Xiang ◽  
Jian Zhao ◽  
Junle Qu ◽  
Jun Song ◽  
Lele Li
2021 ◽  
Vol 12 (1) ◽  
Qingqing Yin ◽  
Anni Pan ◽  
Binlong Chen ◽  
Zenghui Wang ◽  
Mingmei Tang ◽  

AbstractNanoparticle internalisation is crucial for the precise delivery of drug/genes to its intracellular targets. Conventional quantification strategies can provide the overall profiling of nanoparticle biodistribution, but fail to unambiguously differentiate the intracellularly bioavailable particles from those in tumour intravascular and extracellular microenvironment. Herein, we develop a binary ratiometric nanoreporter (BiRN) that can specifically convert subtle pH variations involved in the endocytic events into digitised signal output, enabling the accurately quantifying of cellular internalisation without introducing extracellular contributions. Using BiRN technology, we find only 10.7–28.2% of accumulated nanoparticles are internalised into intracellular compartments with high heterogeneity within and between different tumour types. We demonstrate the therapeutic responses of nanomedicines are successfully predicted based on intracellular nanoparticle exposure rather than the overall accumulation in tumour mass. This nonlinear optical nanotechnology offers a valuable imaging tool to evaluate the tumour targeting of new nanomedicines and stratify patients for personalised cancer therapy.

2008 ◽  
Vol 180 (2) ◽  
pp. 427-441 ◽  
Angélique Millon-Frémillon ◽  
Daniel Bouvard ◽  
Alexei Grichine ◽  
Sandra Manet-Dupé ◽  
Marc R. Block ◽  

Cell migration is an integrated process requiring the continuous coordinated assembly and disassembly of adhesion structures. How cells orchestrate adhesion turnover is only partially understood. We provide evidence for a novel mechanistic insight into focal adhesion (FA) dynamics by demonstrating that integrin cytoplasmic domain–associated protein 1 (ICAP-1) slows down FA assembly. Live cell imaging, which was performed in both Icap-1–deficient mouse embryonic fibroblasts and cells expressing active β1 integrin, shows that the integrin high affinity state favored by talin is antagonistically controlled by ICAP-1. This affinity switch results in modulation in the speed of FA assembly and, consequently, of cell spreading and migration. Unexpectedly, the ICAP-1–dependent decrease in integrin affinity allows cell sensing of matrix surface density, suggesting that integrin conformational changes are important in mechanotransduction. Our results clarify the function of ICAP-1 in cell adhesion and highlight the central role it plays in the cell's integrated response to the extracellular microenvironment.

2021 ◽  
Vol 22 (13) ◽  
pp. 6845
Rebecca L. Pratt

The buzz about hyaluronan (HA) is real. Whether found in face cream to increase water volume loss and viscoelasticity or injected into the knee to restore the properties of synovial fluid, the impact of HA can be recognized in many disciplines from dermatology to orthopedics. HA is the most abundant polysaccharide of the extracellular matrix of connective tissues. HA can impact cell behavior in specific ways by binding cellular HA receptors, which can influence signals that facilitate cell survival, proliferation, adhesion, as well as migration. Characteristics of HA, such as its abundance in a variety of tissues and its responsiveness to chemical, mechanical and hormonal modifications, has made HA an attractive molecule for a wide range of applications. Despite being discovered over 80 years ago, its properties within the world of fascia have only recently received attention. Our fascial system penetrates and envelopes all organs, muscles, bones and nerve fibers, providing the body with a functional structure and an environment that enables all bodily systems to operate in an integrated manner. Recognized interactions between cells and their HA-rich extracellular microenvironment support the importance of studying the relationship between HA and the body’s fascial system. From fasciacytes to chronic pain, this review aims to highlight the connections between HA and fascial health.

2011 ◽  
Vol 6 (10) ◽  
pp. 1117-1126 ◽  
Zuyong Xia ◽  
Yun Xing ◽  
Jongho Jeon ◽  
Young-Pil Kim ◽  
Jessica Gall ◽  

2019 ◽  
Fabrice Senger ◽  
Amandine Pitaval ◽  
Hajer Ennomani ◽  
Laetitia Kurzawa ◽  
Laurent Blanchoin ◽  

Cell and tissue morphogenesis depend on the production and spatial organization of tensional forces in the actin cytoskeleton. Actin network architecture is complex because it is made of distinct modules in which filaments adopt a variety of organizations. The assembly and dynamics of these modules is well described but the self-organisation rules directing the global network architecture are much less understood. Here we investigated the mechanism regulating the interplay between network architecture and the geometry of cell’s extracellular environment. We found that α-actinin, a filament crosslinker, is essential for network symmetry to be consistent with extracellular microenvironment symmetry. It appeared to be required for the interconnection of transverse arcs with radial fibres to ensure an appropriate balance between forces at cell adhesions and across the entire actin network. Furthermore, the connectivity of the actin network appeared necessary for the cell ability to integrate and adapt to complex patterns of extracellular cues as they migrate. Altogether, our study has unveiled a role of actin-filament crosslinking in the physical integration of mechanical forces throughout the entire cell, and the role of this integration in the establishment and adaptation of intracellular symmetry axes in accordance with the geometry of extracellular cues.

Peter C. Y. Chen ◽  
Sahan C. B. Herath ◽  
Dong-an Wang ◽  
Kai Su ◽  
Kin Liao ◽  

The mechanical properties of the microstructures surrounding cells influence the behavior of cells in differentiation, proliferation, and apoptosis, etc. The stiffness of the extra-cellular microenvironment has been shown to be one such mechanical property [1][2]. Studies reported in the literature concerning the stiffness of the extracellular microenvironment mainly sought to understand the scientific principles and mechanisms underlying its effect on cell-environment interaction [3]. This paper describes an approach that achieves such manipulation, and reports experimental results that demonstrate the effectiveness of this proposed approach.

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