Multiple particle tracking (MPT) using PEGylated nanoparticles reveals heterogeneity within murine lymph nodes and between lymph nodes at different locations.
Multiple particle tracking (MPT) using PEGylated nanoparticles reveals heterogeneity within murine lymph nodes and between lymph nodes at different locations.
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DOI：
10.1039/d2bm00816e
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发表时间：
2022-12-06
影响因子：
6.6
通讯作者：
Maisel, Katharina
中科院分区：
文献类型：
--
作者：
Ramirez, Ann;Merwitz, Brooke;Lee, Hannah;Vaughan, Erik;Maisel, Katharina
淋巴结（LNs）是高度结构化的淋巴器官，分别在外皮层和内副皮层分隔B细胞和T细胞，并由富含胶原的网状网络支持。组织材料的特性，如细胞外空间内材料的粘弹性和扩散及其对细胞行为和治疗递送的影响，是最近研究的主题。在这里，我们开发了一种纳米颗粒系统，通过多颗粒跟踪（MPT）结合LN片培养来研究流变性能，包括孔径和粘弹性。聚乙二醇（PEG）的致密涂层允许纳米颗粒在LN细胞外空间内扩散。尽管B细胞区和T细胞区功能不同，但我们发现皮层和副皮层的细胞外组织特性和网格间距没有显著变化，尽管纳米颗粒在B细胞区扩散略有减少。有趣的是，我们的数据表明，LN的孔径小于先前预测的10-20 μm，孔径范围为500 nm-1.5 μm。我们的研究还证实了LNs具有粘弹性特性，具有初始的类似固体的响应，随后在更高的频率下出现应力松弛。最后，我们发现纳米颗粒的扩散取决于LN的位置，与肠系膜LN相比，皮肤引流LN中的纳米颗粒具有更高的扩散系数和孔径。我们的数据揭示了LN间质组织特性、孔径，并定义了纳米颗粒在LN间质中扩散所需的表面化学参数。我们的研究也为研究LN间质提供了工具，并为LN间质靶向纳米颗粒的设计提供了标准。
Lymph nodes (LNs) are highly structured lymphoid organs that compartmentalize B and T cells in the outer cortex and inner paracortex, respectively, and are supported by a collagen-rich reticular network. Tissue material properties like viscoelasticity and diffusion of materials within extracellular spaces and their implications on cellular behavior and therapeutic delivery have been a recent topic of investigation. Here, we developed a nanoparticle system to investigate the rheological properties, including pore size and viscoelasticity, through multiple particle tracking (MPT) combined with LN slice cultures. Dense coatings with polyethylene glycol (PEG) allow nanoparticles to diffuse within the LN extracellular spaces. Despite differences in function in B and T cell zones, we found that extracellular tissue properties and mesh spacing do not change significantly in the cortex and paracortex, though nanoparticle diffusion was slightly reduced in B cell zones. Interestingly, our data suggest that LN pore sizes are smaller than the previously predicted 10–20 μm, with pore sizes ranging from 500 nm–1.5 μm. Our studies also confirm that LNs exhibit viscoelastic properties, with an initial solid-like response followed by stress-relaxation at higher frequencies. Finally, we found that nanoparticle diffusion is dependent on LN location, with nanoparticles in skin draining LNs exhibiting a higher diffusion coefficient and pore size compared to mesenteric LNs. Our data shed new light onto LN interstitial tissue properties, pore size, and define surface chemistry parameters required for nanoparticles to diffuse within LN interstitium. Our studies also provide both a tool for studying LN interstitium and developing design criteria for nanoparticles targeting LN interstitial spaces.
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影响因子：
3.5
作者：
Humphries DL;Grogan JA;Gaffney EA
通讯作者：
Gaffney EA
影响因子：
30.5
作者：
Horsnell, Harry L.;Tetley, Robert J.;De Belly, Henry;Makris, Spyridon;Millward, Lindsey J.;Benjamin, Agnesska C.;Heeringa, Lucas A.;de Winde, Charlotte M.;Paluch, Ewa K.;Mao, Yanlan;Acton, Sophie E.
通讯作者：
Acton, Sophie E.
影响因子：
64.8
作者：
Esterhazy, Daria;Canesso, Maria C. C.;Mucida, Daniel
通讯作者：
Mucida, Daniel
影响因子：
9.8
作者：
Knoblich K;Cruz Migoni S;Siew SM;Jinks E;Kaul B;Jeffery HC;Baker AT;Suliman M;Vrzalikova K;Mehenna H;Murray PG;Barone F;Oo YH;Newsome PN;Hirschfield G;Kelly D;Lee SP;Parekkadan B;Turley SJ;Fletcher AL
通讯作者：
Fletcher AL
DOI：
10.1007/s11481-013-9470-8
发表时间：
2013-09
期刊：
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
影响因子：
--
作者：
Laman JD;Weller RO
通讯作者：
Weller RO