Directed Cell Motility Along Gradients in Extracellular Matrix Fiber Alignment

细胞外基质纤维排列中沿梯度的定向细胞运动

• 批准号: 10681382
• 负责人: Vinay V Abhyankar
• 金额: $ 18.5万
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10681382
• 关键词: 3-Dimensional; Behavior; Biochemical; Biophysics; Biopolymers; Cells; Chemicals; Chemotaxis; Collaborations; Collagen; Collagen Fiber; Collagen Type I; Complex; Controlled Environment; Cues; Development; Disease; Endothelial Cells; Endothelium; Engineering; Environment; Event; Exhibits; Extracellular Matrix; Fiber; Funding; Gel; Goals; Growth; Heterogeneity; Immune; Invaded; Knowledge; Malignant Neoplasms; Mentors; Methods; Microfluidics; Outcome; Population; Positioning Attribute; Process; Property; Reproducibility; Signal Transduction; Speed; Statistical Data Interpretation; Techniques; Testing; Tissues; Traction; Travel; Vascularization; Work; angiogenesis; biophysical properties; built environment; cancer cell; career; cell motility; density; mechanical force; migration; recruit; response; success; therapeutic development; trafficking

Project Summary In native tissue, cell recruitment and positioning are controlled by directed migration, where cells sense multiple guidance cues in their microenvironment and migrate preferentially toward or away from particular signals. Although several types of guidance or "taxis" cues have been identified, the hierarchy between simultaneously presented signals during directed migration remains poorly understood. Dissecting these relationships will help enhance our understanding of cell motility in complex environments with broad implications in therapeutic development to promote or inhibit migratory activity. To expand our knowledge about the cues that promote directed cell migration, we propose a new experimental platform that combines microengineered fiber alignment gradients with controlled soluble biochemical gradients to endothelial, immune, and cancer cell migration within a complex 3D environment. Our platform will allow us to uniquely expose cell populations to a controlled multi-cue 3D environment containing alignment gradients and biochemical gradients to dissect how cells prioritize and respond to simultaneous guidance cues. We hypothesize synergetic (additive) and hierarchal (competitive) relationships between biophysical and biochemical guidance cues that influence directed cell migration. To test this hypothesis, we will carry out the following aims: 1) Quantify migration within a microengineered 3D collagen gel environment with tunable alignment landscapes, 2) Create biochemical gradients and quantify chemotactic responses within 3D gel environments, and 3) Quantify motility responses within combined biophysical and biochemical gradient environments. Success in this project will establish a platform to uniquely study how cells sense, prioritize, and migrate in response to multiple guidance cues (here, biophysical and biochemical gradients), with relevance to early development, immune cell trafficking, vascularization, and cancer invasion.

项目摘要 在天然组织中，细胞募集和定位由定向迁移控制，其中细胞感 其微环境中的多个指导提示并优先向特定迁移或偏离特定 信号。尽管已经确定了几种类型的指导或“出租车”线索，但是 在定向迁移期间同时提出的信号仍然很少理解。解剖这些 关系将有助于增强我们对复杂环境中细胞运动的理解 在治疗发展中促进或抑制迁移活性的意义。 为了扩大我们对促进定向细胞迁移的线索的了解，我们提出了一个新的实验 将微工程化的纤维对齐梯度与受控可溶性生化的平台 在复杂的3D环境中，内皮，免疫和癌细胞迁移的梯度。我们的平台 将使我们能够唯一将细胞群体暴露于包含对齐的受控的多提示3D环境 梯度和生化梯度，以剖析细胞如何优先级和响应同时指导 提示。我们假设生物物理和层次结构（添加词）和层次（竞争性）关系 影响定向细胞迁移的生化引导线索。为了检验这一假设，我们将执行 以下目的：1）量化微型工程的3D胶原蛋白凝胶环境中的迁移 对齐景观，2）创建生化梯度并量化3D凝胶中的趋化反应 环境和3）量化合并生物物理和生化梯度内的运动响应 环境。 该项目的成功将建立一个平台，以唯一研究细胞的感觉，优先级和迁移 对多个指导提示的响应（这里是生物物理和生化梯度），与早期有关 发育，免疫细胞运输，血管化和癌症侵袭。