CAREER: Design Principles of Deformable and Adhesive Particles in Multiphase Flow through Microchannels

细胞在健康和患病状态下表现出不同的机械特性，为生物医学等工程应用中利用物理原理提供了巨大的机会。纳米颗粒通常用于修饰细胞生物学，但其对生理流动环境中细胞力学和运动的影响尚不清楚。该职业奖旨在了解粘附在白细胞表面的纳米颗粒如何影响细胞的可变形性和从血液微循环向炎症组织的迁移。生物物理模型和微流体实验的结合将用于生成工程细胞药物载体的基础知识和设计规则。综合教育计划将通过在各个层面提供丰富的学习经验来传播研究成果：例如，为K-12学生提供全国推广计划，为本科生和研究生提供新的跨学科教学实例，以及为公众提供科学传播。在多尺度力学和粘接性能与微尺度流动中的颗粒输运之间存在着关键的知识鸿沟，这阻碍了建筑材料的发展。该奖项旨在测试药物纳米颗粒在多个长度尺度上影响白细胞的机械和粘附特性的假设，从而通过三个主要运输步骤调节药物有效载荷到炎症部位的输送和治疗效果：小血管的横流运动；生理剪切作用下血管表面的滚动和粘附；通过小孔隙的跨内皮迁移。与生物医学研究中常用的体内技术相比，该奖项明确模拟纳米颗粒和细胞膜之间的物理相互作用，以检查多尺度变形；微流控细胞培养再现了体外血管粘附和运输的动力学。这种体外硅片方法将阐明白细胞运输的基本机制，并有效地探索纳米颗粒的多维参数空间（例如，形状、大小、硬度、浓度和粘附强度）。相图和在宽参数范围内生成的多尺度结构-性质关系将作为一种强大的高通量平台技术，用于设计针对各种物种、疾病和药物管理方法的药物载体。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Cells exhibit varying mechanical properties at healthy and diseased states, presenting enormous opportunities to harness physical principles in engineering applications such as biomedicine. Nanoparticles are commonly used to modify cell biology, but their influence on cell mechanics and movement in a physiological flow environment is poorly understood. This CAREER award aims to understand how nanoparticles adhered to leukocyte surfaces influence cell deformability and migration from blood microcirculation to inflamed tissues. A combination of biophysical models and microfluidic experiments will be used to generate both fundamental knowledge and design rules for engineering cellular drug carriers. The integrated education plan will disseminate research findings by providing enriching learning experiences at various levels: e.g., a nationwide outreach program for K-12 students, new interdisciplinary teaching examples for undergraduates and graduates, and science communications for the public.There exists a critical knowledge gap between multiscale mechanical and adhesive properties and particle transport in microscale flows, hindering the development of architected materials. This award aims to test the hypothesis that drug nanoparticles influence leukocyte mechanical and adhesive properties across multiple length scales, thus modulating the delivery of drug payload to the site of inflammation and therapeutic efficacy through three major transport steps: crossflow movement in small blood vessels; rolling and adhesion on the vascular surface under physiological shear; transendothelial migration through small pores. In contrast to in vivo techniques commonly used in biomedical research, this award explicitly models the physical interaction between nanoparticles and cell membranes to examine multiscale deformations; a microfluidic cell culture recapitulates the kinetics of vascular adhesion and transport in vitro. This in silico-in vitro approach will elucidate fundamental mechanisms of leukocyte transport and efficiently explore a multi-dimensional parameter space for nanoparticles (e.g., shape, size, rigidity, concentration, and adhesion strength). Phase diagrams and multiscale structure-property relationships generated over a broad parameter range will serve as a robust and high throughput platform technology to design drug carriers tailored for various species, diseases, and drug administration methods.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.