This video is one of the first times I thought biology was “cool.” It shows a neutrophil cell chasing a bacterium. Originally recorded in the 1950s by David Rogers at Vanderbilt University, the video gave me a deeper appreciation for life, even at the level of a single cell, because the neutrophil's movements seem so intentful, purposeful, aware. It wasn’t until recently, though, that I actually tried to demystify the neutrophil’s movements and understand how they happen. Here's what I learned: 1. The neutrophil's surface has thousands of protein receptors. Molecules secreted by the bacteria collide with these receptors. When that happens, the proteins change shape, slightly, and initiate a signaling cascade. 2. The neutrophil “knows” where to go because of a discrepancy in bound vs. unbound receptors. The side of the cell closest to the microbe will, probabilistically, have more "bound" receptors than the other side (because the molecules secreted by the microbe have a concentration gradient). This is how the neutrophil figures out which way to move. 3. Each bound receptor activates several G proteins located inside the cell membrane. Each G protein, in turn, switches on PI3K enzymes. In this way, the original signal is amplified; a single "activated" receptor might cause ~100 copies of PI3K to get switched on downstream. 4. The PI3K enzymes stick phosphates onto lipids in the cell membrane. The side of the neutrophil facing the bacterium now has more phosphates than the "back" side. Phosphate-binding proteins, such as GEF, accumulate and then recruit Rac, thus activating it. Rac, in turn, acts like a molecular switch, ultimately recruiting Arp2/3. (TL;DR: A bunch of proteins get activated, and the high phosphate concentration at the leading edge is the key signal for all this.) 5. At any given moment, the neutrophil has millions of actin molecules. These are the proteins used to build the cytoskeleton. Half of the actins are already “assembled” into filaments, but the other half are just floating around. Arp2/3 acts as a nucleator, grabbing onto actin and then starting a new cytoskeletal branch. More actin is assembled at the leading edge (where the Arp2/3 has accumulated), where they each push on the cell membrane with ~2 piconewtons of force. Hundreds of actin chains, pushing together, causes the cell to form protrusions. 6. The assembling actin chains push the cell at a speed of ~20 micrometers per minute (the length of about ten E. coli cells placed end-to-end.) As all of this is happening, another signaling cascade, nucleated at the back end of the cell, is dismantling actin filaments and recycling them. All this happens over a span of about 30 seconds. Much of this process is invisible; what we see, instead, is "just" a cell chasing its prey. But that's the wonderful thing about biology: A singular observation is usually more than enough fodder for a lifetime of work. The well is deep. There is always more to learn.