Biological microswimmers: From signaling to 3D beat to 3D swimming.

生物微游泳者是由细胞体--称为纤毛或鞭毛--突出的细丝节拍推动的。节拍的频率和波形由细胞内信使的变化，特别是钙离子的变化控制。微泳者通常在化学或物理刺激的梯度下进行定向运动，这一过程分别称为趋化性或趋光性。目前尚不清楚刺激功能如何转变为细胞反应模式，这种反应如何控制鞭毛跳动的时空模式，最后，跳动波形最终如何导致刺激梯度中的导航--或许细菌除外。在这里，我们要研究的是航行中自由游动、不受限制的精子在化学梯度中的化学吸引剂。我们使用海胆、人类和老鼠的精子。特别是，我们希望使用(1)化学工具(笼式化学吸引剂)来快速建立定义良好的化学梯度，(2)数字全息显微镜在3D中完全解析鞭毛跳动并记录3D游泳路径，以及(3)当在化学吸引剂的梯度中导航时，同时记录信号事件，例如单个精子细胞中钙离子浓度的变化。因此，我们的目标是提供对细胞运动和导航的逻辑、细胞甚至分子基础以及物理原理的基本见解。如果成功，这一系列技术还将允许在不同的梯度下精确跟踪其他微泳运动员。

Biological microswimmers are propelled by the beat of thin filaments protruding from the cell body - called cilia or flagella. The frequency and waveform of the beat is controlled by changes in intracellular messengers, in particular Ca2+. Microswimmers often undergo directed movement in the gradient of a chemical or physical stimulus, a process called e.g. chemotaxis or phototaxis, respectively. It is not known - perhaps with the exception of bacteria - how the stimulus function is transformed to a cellular response pattern, how this response controls the spatio-temporal pattern of the flagellar beat and, finally, how the beating waveform eventually leads to navigation in a stimulus gradient. Here, we want to study navigation of freely swimming, unrestricted sperm in a chemical gradient of the chemoattractant. We use sperm from the sea urchin Arbacia punctulata, humans, and mice. In particular, we want to employ (1) chemical tools (caged chemoattractants) to rapidly establish well-defined chemical gradients, (2) digital holographic microscopy to fully resolve in 3D the flagellar beat and record the 3D swimming path, and (3) simultaneously record signaling events, e.g. changes in Ca2+ concentration in single sperm cells, while navigating in a gradient of the chemoattractant. Thereby, we aim to provide fundamental insight into the logics of cellular locomotion and navigation, the cellular or even molecular underpinnings, and the physical principles. If successful, this armory of techniques will also allow to precisely track other microswimmers in different gradients.