CAREER: Numerical Methods and Biomechanical Models for Sperm Motility

哺乳动物的精子必须穿过雌性生殖道，游过超过自身长度1000倍的距离才能到达卵子并使其受精。为了帮助治疗精子活力降低，了解精子鞭毛与生殖道不同区域的相互作用是很重要的。特别是，液体流动有助于将卵子带到子宫(与精子进程相反的方向)。最近的实验表明，很大比例的精子表现出正的血液流变性，即重新定位并在背景流中游泳的能力。此外，精子会与输卵管壁结合和解除结合，背景流在精子分离中的作用尚不清楚。该项目的主要科学目标包括进一步分析现有的实验数据(通过图像处理技术)和开发新的计算模型，以了解通过女性生殖道迁移以及在背景流中精子结合和从壁上分离的临床重要性。将开发几个新的计算建模框架，以允许在背景流和墙存在的情况下模拟精子。PI将为几名学生(本科生和研究生)以及一名博士后提供计算生物流体、实验电影图像处理和模型开发领域的跨学科培训。此外，PI将致力于开发图像处理和建模模块，用于地区高中和WPI高中学生的暑期计划。精子鞭毛是一种弹性结构，沿着它的长度传播弯曲的波浪，推动自己穿过女性生殖道。了解精子、动态弹性结构及其周围液体之间相互作用的行为将有助于揭示其三维运动的生物物理学，并将有助于确定在背景流中通过女性生殖道迁移的临床重要性。模型将能够描述精子滚动、鞭毛波形类型、生物化学和液体粘度等因素对精子向前发展的重要性。在这个项目中，PI将把精子鞭毛建模为能够弯曲和扭曲的基尔霍夫杆。杆可以实现平面和非平面波形，并且杆的旋转可以通过与鞭毛中心线上的每个物质点相关联的正交化三轴来捕捉。通过这项工作，PI将专注于以下目标：(1)了解不同粘度的背景流中精子的紧急波形和轨迹的类型；(2)确定滚动是否是由于钙介导的鞭毛波形的变化、背景流、壁面相互作用或与其他精子的流体动力学作用；(3)研究背景流体流动在精子与壁面附着/脱离中的作用；(4)扩展现有的数值方法。PI的研究将导致开发两种新的数值方法来研究墙附近的相互作用，并通过结构的参数表示来提高力计算的精度。这些新开发的方法也可以用于其他细长的弹性结构，如纤毛和细菌鞭毛。

Mammalian sperm must navigate the female reproductive tract, swimming a distance greater than 1000 times their own length to reach and fertilize the egg. In order to aid in the treatment of reduced sperm motility, it is important to understand interactions of the sperm flagellum with different regions of the reproductive tract. In particular, fluid flow helps bring the egg to the uterus (in the opposite direction of sperm progression). Recent experiments have shown that a large percentage of sperm exhibit positive rheotaxis, the ability to reorient and swim against a background flow. Additionally, sperm will bind and unbind to the oviductal wall and the role of a background flow on sperm detachment is not known. The main scientific goals of this project include further analyzing existing experimental data (through image processing techniques) and developing new computational models to understand the clinical importance of migration through the female reproductive tract and sperm binding and detachment from walls in a background flow. Several new computational modeling frameworks will be developed to allow simulations of sperm in the presence of a background flow and a wall. The PI will provide interdisciplinary training for several students (undergraduate and graduate) as well as one postdoc in the areas of computational biofluids, image processing of experimental movies, and model development. In addition, the PI will work to develop image processing and modeling modules to be used in area High Schools and at summer programs for High School students at WPI. The sperm flagellum is an elastic structure that propagates waves of bending along its length to propel itself through the female reproductive tract. Understanding the behavior of the interaction between sperm, dynamic elastic structures, and their surrounding fluid will shed light onto the biophysics of their 3-dimensional motion and will help determine the clinical importance of migration through the female reproductive tract in a background flow. Models will be able to delineate the importance of factors such as sperm rolling, types of flagellar waveforms, biochemistry, and fluid viscosity for forward progression of the sperm. In this project, the PI will model the sperm flagellum as a Kirchhoff rod that is able to bend and twist. The rod is able to achieve both planar and nonplanar waveforms and the rotation of the rod can be captured via an orthonormal triad associated with each material point along the centerline of the flagellum. Through this work the PI will focus on the following objectives: (1) Understand the types of emergent waveforms and trajectories of sperm in a background flow at different viscosities; (2) Determine if rolling is due to calcium mediated changes in flagellar waveforms, background flow, wall interactions, or hydrodynamic interactions with other sperm; (3) Investigate the role of background fluid flow on attachment/detachment of sperm to walls; (4) Extend current numerical methods. The PI's research will lead to the development of two new numerical methods to study interactions near a wall and increase accuracy of force calculations through parametric representations of the structure. These newly developed methods can also be used for other slender elastic structures such as cilia and bacterial flagella.