Researchers has defined a novel 'microtube'-based platform to study how tubular organs, such as the heart and the kidneys, form under the various topographical restrictions commonly experienced inside the body. This study was published in Nature Communications.

The number of people suffering from diseases like atherosclerosis, kidney and liver failure is on the rise worldwide. Although these potentially life-threatening diseases affect different parts of the body, they all arise due to defects in the formation of epithelial tubes — a fundamental type of tissue that makes up many of our organs in addition to the heart, kidneys or liver.

How epithelial tubes form

Epithelial tubes are cylindrical structures that are made of a single or many layers of epithelial cells. Serving as pipelines throughout the body's organs and tissues, epithelial tubes have important physiological roles, from the delivery of essential gases, liquids, and macromolecules around the body to the elimination of metabolic waste.

These structures are formed in the earliest stages of embryonic development, when groups of cells arrange themselves around a central hollow space known as a lumen. Recently, evidence has emerged to show that the physical environment inside our body has a major influence in how all tissues, including epithelial tubes, form, and this has spurred researchers to seek new approaches to studying these old problems.

A three-dimensional (3D) 'microtube' platform for studying lumen formation

To overcome this shortcoming, Prof Lim's team employed an advanced, yet simple technique called microfabrication to synthesise three-dimensional, micron-sized tubular channels that they refer to as microtubes. To test if the physical properties of the microtubes had any influence on the ability of cells to form lumen-containing structures inside.

Researchers introduced a single variable physical parameter. They created microtubes of different sizes, ranging in diameter from 25-250 microns. The highly confined spaces inside the narrower tubes forced the cells to move slowly. The cells often seemed to fluctuate between backward and forward movements, which further slowed down their movement.

Often, the cells in our body must move through highly constrained spaces to rearrange into various structures like tubes. Such conditions, in combination with molecular and genetic factors, ensure that tubes of diverse shapes and sizes are formed in the correct manner across various organs.

The simple microtube platform described in this study provides researchers with crucial insights into the underlying mechano-physiology that governs the arrangement of cells into tubular organs during development. More importantly, it will also help theorise how extreme physical constraints caused by certain pathological conditions could lead to erroneous development of the tissue that manifest as many serious, or even, life-threatening diseases.

This knowledge will be vital for the development of novel and efficient treatment strategies that, in addition to targeting aberrant molecular pathways, would also be aimed at counter-acting extreme physical alterations that occur during many such diseases.