Aapo Tervonen: Computer modeling produces new knowledge on epithelial barrier properties and biomechanics
Epithelial tissues form protective barriers in our bodies that separate organs from their environment. These tissues are formed by layers of cells, and many of the epithelial properties and functions depend on the connections between these cells, called cell-cell junctions. These junctions compose multiple components, including the tight junctions – forming a barrier between the cells – and adherens junctions – attaching the cells mechanically to each other.
Many diseases that affect the epithelial tissues lead to dysfunctions in the epithelial barrier properties, especially in the tight junctions. For example, these include inflammatory bowel disease, which is very common in Finland, and age-related macular degeneration, the leading cause of adult blindness in Western countries. In addition to connecting to each other, cells are attached to the material under them, meaning that epithelial cells can transmit forces and thus communicate mechanically between them and their environment. Changes in these mechanical properties of the epithelial tissues and their environment are linked to many pathological conditions, including tumor formation. In fact, most common cancers are of epithelial origin. Basic research in epithelial biophysics is an essential step in understanding these diseases and developing better treatments.
The thesis aimed to improve our understanding of the aspects of epithelial physiology related to the barrier properties and biomechanical communication between the cells by using computational modeling. More specifically, the focus was to study the governing components of the epithelial barrier and especially the tight junctions as well as to study the role of environmental stiffness on the force transmission between the cells.
Various computational methods were utilized in the thesis. These include the steady-state permeability model, multicompartmental model, random resistor network, finite element method, and cell-based model.
The results indicated that the structure of the tight junctions and their structural dynamics have an essential role in determining the whole epithelium's barrier properties. In addition, the computational results revealed that the structural dynamics and changes in them show differently in the two common epithelial barrier measurements: the permeability of specific tracer molecules and the electrical resistance of the epithelium against ionic currents.
The results on the epithelial force transmission demonstrated that the transmission of mechanical forces between epithelium cells becomes more restricted as the stiffness of the material under them becomes higher. Furthermore, the epithelial cells can transmit information on the changes in stiffness, such as sudden changes in local stiffness, over long distances.
The modeling results not only provide a fundamental understanding of epithelial biophysics but also help to guide the experimental work. They create computational platforms to produce testable hypotheses, optimize measurements, and better understand the measurement results. Together with experimental work, computational models of epithelia provide a complete view of the properties and relationship of the epithelial barrier and biomechanics to help us understand these essential tissues in health and in disease.
The doctoral dissertation of M.Sc. (Tech.) Aapo Tervonen in the field of biomedical engineering, titled Computational Modeling of Epithelial Barrier Properties and Biomechanics, will be publicly examined in the Faculty of Medicine and Health Technology at Tampere University at 12 o’clock on Friday 14 January 2022. The Opponent will be Senior Lecturer Dawn Walker from The University of Sheffield, while Professor Jari Hyttinen will act as the custos.