Viruses obey the laws of physics, and understanding these principles opens the path to creating new therapeutic approaches. This text, written in collaboration with Karin Wuertz-Kozak and Maureen Ferran, was originally published on The Conversation website, which collects materials from researchers.
The attraction of biomedical engineers and biologists to mechanobiology—the study of how physical forces affect biology—is partly due to the beauty of physics at the cellular level. Physics is present everywhere: from how artery wall cells react to blood flow, to how vertebral cells support weight, or how lung cells cyclically expand with each breath.
Since every structural element of the body is subjected to specific combinations of physical forces, the viruses that infect it must also interact with these forces. The way viruses interact with these forces influences their ability to infect cells and cause serious diseases.
When microscopic viral particles enter the body, they depend on the mechanism of host cells to continue their life cycle. Many viruses first bind to receptors on the cell surface. The movement of the cell membrane, provided by the internal cytoskeleton, causes it to curve and engulf the invasive particle, forming a tiny vesicle that transports it inside. This process, called endocytosis, leads to the cell absorbing the virus.
After entering, the virus moves through the internal structure of the cell, releases its genetic material, and uses the cellular machinery to produce copies of itself. Then, new viral particles leave the cell to infect neighboring cells.
Each of these stages is inherently physical. The tension of the cell membrane can promote or hinder viral incorporation. The cytoskeleton, which transports these viral particles, is the same structure that cells use to sense and apply pressure to the environment. Furthermore, the stiffness of the cellular environment determines how the cell spreads and organizes, which can alter its susceptibility to the invader.
A healthy person usually recovers quickly from an infection. However, people with pre-existing conditions, such as pulmonary fibrosis—where lung tissue hardens and can no longer fully expand—may have a viral infection worsen their condition. This mechanical predisposition of tissues to infection is one reason healthcare workers advise avoiding contact with the elderly and immunocompromised during illness.
Our lab investigates the mechanobiology of different tissue types to understand how everyday physical stresses can exacerbate diseases. For example, repeatedly lifting and carrying heavy objects can wear down intervertebral discs, and mechanical ventilation can overstretch and damage the lungs.
However, culturing cells on a plastic Petri dish—a standard method in most virology labs—only shows part of the picture. The plastic used for tissue culture is significantly stiffer than living tissue, resembling a working surface more than a lung. Cells perceive this difference during experiments; the stiffness of the environment can influence both their behavior and their response to infection.
To bring the mechanics of the human body into the lab, we culture lung cells on thin layers of a flexible silicone polymer called PDMS, which we tune to match the softness of real lung tissue. These layers are placed in small chambers that cyclically stretch and relax upon computer command, which dictates the degree and duration of stretching. This allows us to simulate the physical movements of breathing.
We can use a genetically modified virus to make infected cells glow red under a microscope, tracking how it spreads between cells. But how do we track changes in cell mechanics during infection? Our team monitors the activity of two important proteins called YAP and TAZ, which act as cell force sensors. When tissue experiences stiffness or tension, these sensors move into the nucleus and activate genes related to growth and repair. In the absence of such forces, as typically occurs in softer tissues, YAP and TAZ remain inactive and outside the nucleus.
It is known that some viruses utilize this same signaling pathway; therefore, studying YAP and TAZ can provide insight into how mechanical forces and infection influence each other. Using the CRISPR gene editing tool, we can attach a fluorescent marker to YAP or TAZ and observe their activation in real time under a microscope as they respond not only to mechanical forces but potentially also to infection.
With this platform, we can better answer questions such as: will lung cells respond differently to infection under various forces? Or will these forces change the efficiency of viral infection? Currently, our preliminary results show that the stiffness of the cellular environment affects the degree of cell infection: lung cells grown on stiffer surfaces, similar to fibrosis, appear to be more heavily infected.
Understanding the mechanics of viral infection is of particular interest to researchers and physicians, given the constant prevalence of respiratory infections worldwide. The common cold, COVID-19, and influenza are just a small fraction of viral infections: it is known that over 200 types of viruses infect humans.
Mechanobiology may be as important for the infection cycle as its biochemical or immunological aspects. Under the microscope, the differences between stiff and congested lung tissue and soft, healthy lung tissue are evident, and viruses can move adaptively in these environments.
As scientists map these mechanical signals, new opportunities emerge for preventing and treating infections. Among these are therapies that can reduce physical stress in tissues, or even biomarkers that can inform patients whether they are susceptible to tissue hardening or certain infection pathways and the potential damage they might cause. The human body is as mechanical as it is chemical, and this applies to the infections it encounters.
