Mimicking white matter tract topography using core-shell electrospun nanofibers to examine migration of malignant brain tumors.
Mimicking white matter tract topography using core-shell electrospun nanofibers to examine migration of malignant brain tumors.
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DOI：
10.1016/j.biomaterials.2013.03.069
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发表时间：
2013-07
期刊：
影响因子：
14
通讯作者：
Winter, Jessica O.
中科院分区：
文献类型：
--
作者：
Rao, Shreyas S.;Nelson, Mark T.;Xue, Ruipeng;DeJesus, Jessica K.;Viapiano, Mariano S.;Lannutti, John J.;Sarkar, Atom;Winter, Jessica O.
多形式胶质母细胞瘤（GBM）是人类最致命的癌症之一，其特点是具有高浸润能力，部分受神经细胞外基质（ECM）调节。开发有效治疗方法的一个主要限制是缺乏模拟GBM迁移高速公路特征的体外模型。理想情况下，这些模型将允许对力学和化学进行可调控制，以允许检查每个组件的独特作用。为了满足这一需求，我们通过核-壳静电纺丝技术开发了排列纳米纤维生物材料，可以系统地研究对细胞粘附和迁移的机械和化学影响。这些模型模拟了白质束的地形，白质束是GBM迁移的主要“公路”。为了独立研究化学和力学对GBM行为的影响，在纳米纤维的“核心”中使用不同的聚合物（即明胶、聚醚砜、聚二甲基硅氧烷）来调节纳米纤维的力学，同时使用常见的聚ε-己内酯（PCL）“外壳”来保持表面化学性质。这些材料显示出GBM对纳米纤维力学的敏感性，单细胞形态（Feret直径）、迁移速度、focal adhesion kinase （FAK）和myosin light chain 2 （MLC2）的表达都与纳米纤维模量有很强的依赖性。同样，使用细胞外基质分子（即透明质酸（HA）、胶原蛋白和基质）调节纳米纤维的化学性质，在“壳”材料中使用常见的PCL“核”来保持机械性能，显示GBM对HA的敏感性；具体来说，是对移民的负面影响。该系统模拟了白质束的地形特征，可以进一步研究调节脑肿瘤行为的力学、化学和地形的复杂相互作用。
Glioblastoma multiforme (GBM), one of the deadliest forms of human cancer, is characterized by its high infiltration capacity, partially regulated by the neural extracellular matrix (ECM). A major limitation in developing effective treatments is the lack of in vitro models that mimic features of GBM migration highways. Ideally, these models would permit tunable control of mechanics and chemistry to allow the unique role of each of these components to be examined. To address this need, we developed aligned nanofiber biomaterials via core–shell electrospinning that permit systematic study of mechanical and chemical influences on cell adhesion and migration. These models mimic the topography of white matter tracts, a major GBM migration ‘highway’. To independently investigate the influence of chemistry and mechanics on GBM behaviors, nanofiber mechanics were modulated by using different polymers (i.e., gelatin, poly(ethersulfone), poly(dimethylsiloxane)) in the ‘core’ while employing a common poly(ε-caprolactone) (PCL) ‘shell’ to conserve surface chemistry. These materials revealed GBM sensitivity to nanofiber mechanics, with single cell morphology (Feret diameter), migration speed, focal adhesion kinase (FAK) and myosin light chain 2 (MLC2) expression all showing a strong dependence on nanofiber modulus. Similarly, modulating nanofiber chemistry using extracellular matrix molecules (i.e., hyaluronic acid (HA), collagen, and Matrigel) in the ‘shell’ material with a common PCL ‘core’ to conserve mechanical properties revealed GBM sensitivity to HA; specifically, a negative effect on migration. This system, which mimics the topographical features of white matter tracts, should allow further examination of the complex interplay of mechanics, chemistry, and topography in regulating brain tumor behaviors.
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DOI：
10.1083/jcb.201108062
发表时间：
2012-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim DH;Provenzano PP;Smith CL;Levchenko A
通讯作者：
Levchenko A
影响因子：
4.1
作者：
Jung, S;Ackerley, C;Rutka, JT
通讯作者：
Rutka, JT
影响因子：
--
作者：
Caspani, Elisabetta M.;Echevarria, Diego;Small, J. Victor
通讯作者：
Small, J. Victor
影响因子：
14
作者：
Chew, Sing Ylan;Mi, Ruifa;Leong, Kam W.
通讯作者：
Leong, Kam W.
影响因子：
2.5
作者：
Blackstone, B. N.;Willard, J. J.;Powell, H. M.
通讯作者：
Powell, H. M.