A moving cell looks simple from a distance. One edge pushes forward, the rest follows, and the whole thing creeps along as if its contents somehow know where to go.<\/p>\n
That neat picture leaves out a crucial detail, according to a new study from Oregon Health & Science University<\/a>. Inside the cell, proteins are not just drifting randomly until they reach the right spot. Instead, the researchers found what they describe as internal “trade winds.” These are streams of fluid that push key proteins toward the cell\u2019s leading edge. This part drives movement, repair and attachment.<\/p>\n The work, published in Nature Communications<\/a>, challenges a long-standing assumption in biology. For years, textbook diagrams have treated many free-floating proteins as passengers of diffusion, moving by chance through the cell\u2019s interior. This study argues that, at least in migrating cells, chance is not doing all the work.<\/p>\n Oregon Health & Science University scientists capture a 3D single-molecule super-resolution microscopy image showing individual actin protein molecules inside a cell, each rendered as a single dot and captured at extraordinary detail \u2014 roughly 10,000 times finer than a human hair. (CREDIT: OHSU\/Christine Torres Hicks) The clue came from a dark line<\/p>\n The finding began with an accident. Catherine Galbraith and James Galbraith, both associate professors in OHSU\u2019s Biomedical Engineering Department and Discovery Engine Investigators in the OHSU Knight Cancer Institute, were teaching a neurobiology course at the Marine Biological Laboratory in Massachusetts<\/a> when something odd happened during a standard experiment.<\/p>\n \u201cIt actually started out as an unexpected finding,\u201d Cathy Galbraith said. \u201cWe were just conducting an experiment with students in class.\u201d<\/p>\n The team had used a laser to bleach proteins in a strip across the back of a living cell<\/a>, making them temporarily invisible. Then a second thin dark line appeared near the front edge of the cell. That was not supposed to happen.<\/p>\n \u201cWe kind of did it for fun and then realized this gave us a way of measuring something that wasn\u2019t able to be measured before,\u201d she said.<\/p>\n That line turned out to mark soluble actin moving rapidly to the cell front. Actin is one of the main proteins that helps cells change shape and crawl. The researchers measured an apparent forward velocity of 3.6 \u00b1 1.1 micrometers per second. This is nearly 50 times faster than the rearward movement of the original bleach line, which was measured at 0.08 \u00b1 0.02 micrometers per second.<\/p>\n More than random drift<\/p>\n To probe what was driving that motion, the team used several imaging methods, including photobleaching, localized photoactivation, single-molecule tracking, fluorescence correlation spectroscopy, 3D structured illumination microscopy and iPALM, a super-resolution imaging technique.<\/p>\n Transport of depolymerized actin to the polymerizing front is facilitated by myosin contraction. (CREDIT: Nature Communications) <\/p>\n They also built an inverse version of a standard fluorescence test and gave it a playful name: FLOP, for Fluorescence Leaving the Original Point.<\/p>\n \u201cIt wasn\u2019t a flop at all,\u201d Cathy Galbraith said. \u201cRather, it was the opposite. It is anything but a flop, because it worked.\u201d<\/p>\n Using these tools in NG108 cells, CAD cells and 3T3 fibroblasts, the researchers found that myosin II contraction helps create a forward fluid flow. When they inhibited myosin activity<\/a>, the directed movement weakened and became more symmetrical. This suggests that the cell\u2019s internal machinery was no longer pushing proteins to the front as effectively.<\/p>\n \u201cWe realized the cartoon models in textbooks were missing a huge piece,\u201d Jim Galbraith said. \u201cThere had to be some kind of flow in the cell pushing things forward. Cells really do \u2018go with the flow.\u2019\u201d<\/p>\n The transport also appeared to be broadly non-specific. It did not move only actin. Proteins involved in protrusion and adhesion, including Arp3, vinculin and paxillin, also showed forward-biased movement toward the leading edge.<\/p>\n A front compartment with its own rules<\/p>\n The study goes further than a simple flow model. The researchers say the cell front acts like a distinct compartment, separated from the main cell body by an actin-myosin condensate barrier. It is not enclosed by a membrane. Therefore, they call it a pseudo-organelle.<\/p>\n Myosin mediates the advective flow of actin. (CREDIT: Nature Communications) <\/p>\n That barrier seems to do two jobs. It slows exchange between the front and the rest of the cell, and it helps aim protein-rich flow toward the parts of the leading edge that are actively advancing.<\/p>\n \u201cWe found that the cell can actually squeeze at the back and target where it sends that material,\u201d Jim Galbraith said. \u201cIf you squeeze half a sponge, the water only goes on that half. That\u2019s basically what the cell is doing.\u201d<\/p>\n The team says the curvature and position of these actin-myosin arcs can shift as the cell changes direction. In laser ablation experiments, disrupting a single arc caused the cell edge directly in front of it to collapse. This points to a local control system rather than a uniform one.<\/p>\n \u201cJust as small shifts in the jet stream can change the weather, small changes in these cellular winds could change how diseases begin or progress,\u201d Cathy Galbraith said.<\/p>\n