Biomedical Engineering Reference
In-Depth Information
also used to indicate adhesion strength. However, these cellular processes exhibit
complex dependencies on adhesive strength and do not provide direct or sensitive
measurements.
To better understand signaling patterns involved in changing the behavior
of cells during disease and development, presenting ECMs in their physiological
form is important. Many implantation studies using biocompatible materials have
shown that the microarchitecture of the materials is the primary determinant in the
foreign body response. Mechanical and biochemical properties of the ECM in the
body are different from the two-dimensional (2D) rigid tissue culture plastic (or
glass) surface often used in cell culture. On a 2D substrate, cells are restricted to
spread and attach to a prefixed ECM coating on the tissue culture plastic. Hence,
the effects of biophysical properties of the matrix that provide a spatiotemporal ef-
fect in the body are not part of the effect. The mechanical nature and composition
of the substrate upon which they grow are critical for cellular activity. Porous ma-
trices of ECM with a different rigidity show that cells respond differently and the
matrix stiffness is an important factor in cellular behavior. Many cell types attach
differently to three-dimensional (3D) matrices than to the 2D culture. Focal adhe-
sions appear distinct in 3D from 2D and are called 3D matrix adhesions to distin-
guish them from their 2D counterparts. Such differences in cell adhesion between
2D and 3D cause different signal transduction and subsequent alteration in cellular
rearrangement. For example, rigid films of collagen promote the cell spreading and
growth of hepatocytes (found in the liver), whereas collagen hydrogels promote a
rounded morphology and differentiated phenotype of the same cells. This could
be via the response of tractional forces between cells and the substrate; a scaffold
should be able to withstand cell contractile forces. Thus, ECM interactions with
the cell are chemical as well as physical, unlike soluble ligands, which are chemical
only.
7.2.4 Cell-CellInteractions
Direct interactions between cells are also important in the development and func-
tion of tissues. Several different types of stable cell-cell junctions are critical to the
maintenance and function of the epithelial barrier. However, some cell-cell inter-
actions are transient, for example, the interactions between cells of the immune
system and the interactions that direct leukocytes to sites of tissue inflammation.
Interactions between the same types of cells are called homotypic interactions and
interactions between two different cell types are termed as heterotypic interactions.
Cell-cell contact sites provide important spatial cues to generate cell polarity and
enable cells to sense and respond to adjacent cells. Junctional complexes at cell-cell
contact sites are also control points for regulating solute flow across cell monolay-
ers (through tight junctions) and from one cell to another (through gap junctions).
During in vitro cell culture, cell seeding density needs to be optimized for prop-
er growth. Most normal diploid cells, with the exception of immortal cell lines,
require a minimum cell seeding density for successful growth in vitro. When cells
proliferate to cover the entire dish, they reach a state of confluency where cell-cell
interactions are maximal. Many normal diploid cells such as fibroblasts respond to
the maximum interactions by slowing or stopping their growth, called the state of
