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

生物微泳者是由从细胞体突出的细丝（称为纤毛或鞭毛）的跳动推动的。搏动的频率和波形由细胞内信使的变化控制，特别是Ca 2+。微泳者通常在化学或物理刺激的梯度中进行定向运动，该过程分别称为趋化性或趋光性。目前尚不清楚--也许细菌除外--刺激功能如何转化为细胞反应模式，这种反应如何控制鞭毛搏动的时空模式，以及最后，搏动波形最终如何导致刺激梯度中的导航。在这里，我们想研究自由游动，不受限制的精子在化学梯度的化学引诱物中的导航。我们使用海胆、人类和老鼠的精子。特别是，我们希望采用（1）化学工具（笼状化学引诱物）来快速建立明确的化学梯度，（2）数字全息显微镜，以完全解析3D鞭毛节拍并记录3D游泳路径，以及（3）同时记录信号事件，例如单个精子细胞中Ca 2+浓度的变化，同时在化学引诱物的梯度中导航。因此，我们的目标是提供基本的洞察细胞运动和导航的逻辑，细胞甚至分子的基础，和物理原理。如果成功的话，这种技术也将允许在不同的梯度中精确地跟踪其他微泳者。

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.