Estimation of cancer cell migration in biomimetic random/oriented collagen fiber microenvironments

Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.

实施小水电代燃料生态工程 实现人与自然和谐发展

光泽县是全国首批100个初级农村电气化达标县,县内有生态公益林保护区40206hm2。发展小水电代燃料生态工程是真正把光泽县建成现代化小康县的富民工程和德政之举。

浅谈农村电网改造导线截面选择方法

本文介绍了农村电网改造导线截面选择两种方法:一是按经济电流密度选择导线截面;二是按允许的电压损耗选择导线截面。并列举一个在农村电网改造中导线截面选择的实例。

浅析小水电工程的投资控制

小水电工程投资是一项综合性、专业性、政策性的活动,涉及面广,贯穿于工程建设的各个阶段。如何搞好水电施工项目成本管理,直接涉及到企业能否在市场竞争中立于不败之地,不断稳步发展的重要问题。有鉴于此,为实现最大的投资效益,本文作者以多年从事小水电工程的经验,浅析几点看法。

Nonlinear dynamics of cell migration in anisotropic microenvironment

Cell migration in anisotropic microenvironment plays an important role in the development of normal tissues and organs as well as neoplasm progression,e.g.,osteogenic differentiation of embryonic stem cells was facilitated on stiffer substrates,indicating that the mechanical signals greatly affect both early and terminal differentiation of embryonic stem cells.However,the effect of anisotropy on cell migration dynamics,in particular,in terms of acceleration profiles which is important for recognizing dynamics modes of cell migration and analyzing the regulation mechanisms of microenvironment in mechanical signal transmission,has not been systematically investigated.In this work,we firstly rigorously investigate and quantify the differences between persistent random walk and anisotropic persistent random walk models based on the analysis of cell migration trajectories and velocity auto-covariance function,both qualitatively and quantitatively.Secondly,we introduce the concepts of positive and negative anisotropy based on the motility parameters to study the effect of anisotropy on acceleration profiles,especially the nonlinear decrease and non-monotonic behaviors.We particularly elaborate and discuss the mechanisms,and physical insights of non-monotonic behaviors in the case of positive anisotropy,focusing on the force exerted on migrating cells.Finally,we analyze two types of in vitro cell migration experiments and verify the universality of nonlinear decrease and the consistence of non-monotonic behaviors with numerical results.We conclude that the anisotropy of microenvironment is the cause of the non-monotonic and nonlinear dynamics,and the anisotropic persistent random walk can be as a suitable tool to analyze in vitro cell migration with different combinations of motility parameters.Our analysis provides new insights into the dynamics of cell migration in complex microenvironment,which also has implications in tissue engineering and cancer research.

Biophysical model for high-throughput tumor and epithelial cell co-culture in complex biochemical microenvironments

The in vivo tumor microenvironment is a complex niche that includes heterogeneous physical structures,unique biochemical gradients and multiple cell interactions.Its high-fidelity in vitro reconstruction is of fundamental importance to improve current understandings of cell behavior,efficacy predictions and drug safety.In this study,we have developed a high-throughput biochip with hundreds of composite extracellular matrix(ECM)microchambers to co-culture invasive breast cancer cells(MDA-MB-231-RFP)and normal breast epithelial cells(MCF-10 A-GFP).The composite ECM is composed of type I collagen and Matrigel which provides a heterogeneous microenvironment that is similar to that of in vivo cell growth.Additionally,the growth factors and drug gradients that involve human epidermal growth factor(EGF),discoidin domain receptor 1(DDR1)inhibitor 7 rh and matrix metalloproteinase inhibitor batimastat allow for the mimicking of the complex in vivo biochemical microenvironment to investigate their effect on the spatial-temporal dynamics of cell growth.Our results demonstrate that the MDA-MB-231-RFP cells and MCF-10 A-GFP cells exhibit different spatial proliferation behaviors under the combination of growth factors and drugs.Basing on the experimental data,we have also developed a cellular automata(CA)model that incorporated drug diffusion to describe the experimental phenomenon,as well as employed Shannon entropy(SE)to explore the effect of the drug diffusion coefficient on the spatial-temporal dynamics of cell growth.The results indicate that the uniform cell growth is related to the drug diffusion coefficient,which reveals that the pore size of the ECM plays a key role in the formation of complex biochemical gradients.Therefore,our integrated,biomimetic and high-throughput co-culture platforms,as well as the computational model can be used as an effective tool for investigating cancer pathogenesis and drug development.

金砖国家的崛起及其发展前景

2001年,美国高盛公司首次提出＂金砖四国＂概念,囊括了全球最大的四个新兴市场国家。＂金砖四国＂（BRIC）引用了巴西、俄罗斯、印度和中国的英文首字母,由于该词与英文中的砖（Brick）类似,因此被称为＂金砖四国＂。2010年12月,＂金砖四国＂一致商定,吸收南非作为正式成员加入＂金砖国家＂合作机制,＂金砖四国＂即变成＂金砖五国＂,并更名为＂金砖国家＂（BRICS）。一、金砖国家崛起的主要特点（一）经济快速增长,