Mechanical modeling at the cellular level including smooth muscle contraction

This project is concerned with chemomechanical modeling on the cellular and sub-cellular level, in particular of smooth muscle cells. The cell is the structural and functional building block of all living units. There are more than 100 different types of cells in the human body and all of these differ in shape, structure and functionality. Some are similar to others while others differ completely. Due to their different structure, function and surrounding environment they all behave mechanically very different. To understand the biomechanical behavior of the cell numerous experiments can be performed. There are several experimental methods available today and with the improving nano-technology to perform mechanical testing on a single cell or on groups of cells more advanced experimental methods develop. With increasing experimental data, better models visualizing the mechanical behavior of cells can be developed. To fully understand the behavior of cells it is important to understand the behavior of sub-cellular units. The cell consists of many different organelles some of these are nucleus, endoplasmic reticulum, Golgi apparatus, mitochondria, membrane, cytosol and the cytoskeleton. From the biomechanical point of view, the cytoskeleton the most important because it is considered to be the load bearing reinforcement of the cell. The mechanical structure of human cells can be compared to modern skyscrapers. Both structures follow the same strategy in the sense that their weight and strength are carried and supported by an interior skeleton, the cytoskeleton. The cytoskeleton of a eukaryotic cell consists mainly of three protein-based polymers: actin filaments, intermediate filaments and microtubules. Some cells such as the erythrocytes may contain fine strings of the cytoskeletal protein spectrin. These polymers all differ in size and the protein they are based on. They are all differently organized in networks and bundles. Today there are many different mechanical models available visualizing various behaviors of the cell. These models depend mainly on what type of cell that is studied and what mechanical experiment it resembles. Mechanical modeling of human cells can be summarized into three different methods, each acting at different length scales. The first method is the polymer-based theory that describes a method to model the cell at the protein level. The second method is the tensegrity model that is based on tensegrity theory and can be used to model larger part of the cell up to whole-cell models. The third method is the continuum-based theory that can be used to model both small parts of the cell as well as larger parts of the cell. What is common for all methods is that they are highly dependent on experiments. There are many aspects of the mechanical behavior of cells that are unknown providing difficulties to develop an accurate mechanical model. However, with more advanced and accurate models we better understand the biological behavior of cells. There are mainly three different types of muscle cells in the human body. Skeletal muscle cells, cardiac muscle cells and smooth muscle cells. All muscle cells have the purpose of contracting and relaxing contributing to movement and stability. Although the mechanical behavior is of all these cells are similar, the muscle cells have very different structure and appearance. The skeletal muscle cell is a voluntary muscle cell, i.e. it is controlled by conscious actions while the cardiac muscle cells and smooth muscle cells are involuntary. The smooth muscle cell is located in the inner wall of internal organs such as stomach and intestines and arteries. In the arteries the smooth muscle cells are located within the media, the middle layer of arteries. It provides structural changes of the different organs where it is located. For example, the smooth muscle is highly involved in the transportation of food to the stomach and the regulation of blood flow within the arteries. The smooth muscle cell has a spindle-like shape with its wide waist in the middle but is almost narrow pointy shapes at the ends. It is about 50 to 200 microns long but only 2 to 10 microns wide. The smooth muscle cell has one nucleus which is located in the center of the cell. The contraction of smooth muscle cells, one key modelling aspect of this project, is obtained through sliding of myosin filaments along actin filaments as in the skeletal muscle cells but in a different structure. In the skeletal muscle the contractile filaments are organized striated and contracts in one direction but within smooth muscles the myosin and actin filaments are organized more evenly and, thereby, giving a contraction in the cell in all directions. Smooth muscle contraction has been studied for several decades but many aspects are not well understood. In particular, aspects concerning the mechanochemical and mechanobiological modelling are still unknown. Smooth muscle contraction is activated through an increase of calcium concentration but the coupling between the actual contraction and chemical activation is also unknown. To better understand the smooth muscle contraction from chemical activation to the mechanical contraction a good mechanochemical model is necessary.