Cellular Forces: Some Biophysics in Simple Words


Within the boundaries of our knowledge about physical world are a couple of most essential dependencies. Functions of every object that is inside are regulated by these two. They are space-time and gravity. An object that is bound within space-time and responsive to gravity experiences physical stress at all times. Cell is no exemption. Like it works in our planetary system or universe in general, this stress can be originated from within a cell or from externally applied forces, or most often, both. This apparently results in intercellular and intracellular dynamics. Every time a cell undergoes such dynamics, it exhibits a variety of biophysical properties such as cellular migration and differentiation.


Our basic know-how of action-reaction concept gives us sufficient insights to realize how vital forces are in controlling cellular functions and behavior. However, only going deeper into a research study of this subject unlocks a vast spectrum of ideas on, 1) how cells act to create forces and, 2) react in responding to forces. During such process, we may also get to know 3) how cells end up translating these physical forces into biochemical signals. This translation at the cellular level is known as mechanotransduction. Cellular dynamics are so quick in space-time that our investigation becomes harder as the number of cells in observation increases, particularly if we have to deal with living cells. Measuring incredibly dynamic cellular forces inside out involves a lot of methodologies, but we shall understand one of them, as follows.


For instance, consider the concept of blood circulation. Circulatory system requires blood vessels, the loops that allow blood flow throughout the body. These vessels are of three types – arteries that direct blood from the heart, capillaries that allow mixture of blood with the necessary chemical contents, and veins that bring blood back to the heart for filtration. Let us now zoom our focus at the surface of a blood vessel. Like our skin layers, blood vessels have layers around them, like a tube in a tube in a tube. Closely observing one of them reveals a thin layer formed by smaller objects. Those small objects are the endothelial cells. This layer, called endothelium, looks like a barrier between flowing blood and the actual vessel wall.


There are two very significant reasons why we need this barrier. One, the cells, that form this barrier ensure that the flowing blood is not mixed with anything unnecessary from the surrounding medium. As part of this task, they also prevent all components that need to stay with the flowing blood from escaping out. Two, it is the responsibility of these cells to regulate the blood pressure. The health issues that we hear in our daily life such as inflammation, tissue swelling, blood clotting, BP instability, etc. occur when these cells fail in their functional execution, of course, conditions apply. After such a depiction, it is easy to realize that when the endothelial cells change their position allowing compression or expansion of a blood vessel width, the blood flow gets disrupted leading to several complications. Often such changes in endothelium barrier occur due to shear stress created when blood flows along vessel walls and a few of weak cells are pulled or pushed by the flow.

Ever heard of next generation sequencing of genomes? Although a totally different ballgame with a few common modalities, scientists, at the departments of bioengineering and mechanical engineering of the University of Washington, have made the so far impossible possible. The superior task of measuring cellular forces within a collection of living endothelial cells (unlike the conventional single cell studies) calls for an equally superior technology and science, an old hindrance that is now attacked. An attempt to write about their research work in (unacceptably) layman language is made here.


A matrix of closely spaced vertical silicone posts, called micropost array, is employed enabling target cultured cells to get glued across multiple posts, forming a monolayer over the micropost (Christopher Chen; Nature Methods, 7:733-36, 2010). The posts are designed to be spring-like flexible proportional to the quantity of cells being examined, that the posts bend as per the force applied by the cells, in the process of attaching to them. The bend in the posts is made measurable using a microscopy whereby, the forces are mathematically measured. In such an arrangement, some microfluids are allowed to flow through. The flow is, of course, measurable. Now, scientists introduced an obstacle in the cell-formed layer so as the flow gets disrupted. Using this system, scientists observed disturbed and laminar flows of microfluids across the cell-layer, which enabled their understanding of how cells respond to a variety of flow conditions. If cells couldn’t stick together strong enough to withstand the introduced flow, that is when one gets to derive the biomechanical reasons behind several health complications raised due to cellular forces and their response to external forces. With such grand vision, their research is now one of the most significant answers to a bunch of medical questions (Am J Physiol Heart Circ Physiol, 302:H2220-29, 2012).


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