Biomedical Engineering Reference
In-Depth Information
vasculature and heart muscle in response to hypertension [49] are potential detrimental
mechanoresponsive effects. However, here the focus will be on positive mechanotransduction
to allow control of cell fate in a desired manner [50].
After the discovery of stem cells, understanding the best way for manipulation, stimula-
tion, or conduction of them has been a major scientific focus [51, 52]. Research on the effect
of chemical, matrix stiffness, topography, electrical, magnetic, and mechanical stimuli on
stem-cell behavior have been considered and some of these approaches will be described
with a particular focus on topographical and mechanical stimulation [52-56]. It is noted that
many different types of mechanical stimuli, in combination or individually, have been tried
previously. These include stretching forces [57], compression [58], shear stress [59], and
vibration [60, 61], with results demonstrating that type of stimulus, time-scale, and amplitude
are all important [62-64].
Mechanotransduction
For the purposes of this chapter, mechanical stimulation will be referred to as mechano-
transduction, although it is acknowledged that mechanotransduction can be initiated
by a wide variety of stimuli that differentially regulate intracellular tension and cell
morphology, which will be discussed in parallel (e.g., material surfaces). The molecular
response of cells to any mechanical stimulus usually is in the form of altered protein pro-
duction and changing phenotype. This occurs through a process called mechanotrans-
duction, and this is a type of adaptation that is necessary for cellular life [65]. Briefly, the
process starts by sensing changes in the external environment, transfer of this mechanical
message by cytoskeleton to the nucleus evokes a chromosomal response to the stimulus, which
will affect transcript to protein synthesis: this may be in the form of indirect (biochemical) or
direct (mechanical) stimulation [47, 66]. Various mechanisms are involved in the mecha-
notransductive process. These responses start at the cellular level and are usually driven
by cell-matrix interactions, adhesions, as a start point - or at least adhesions are a
mechanism with particular interest in the field [67]. Indirect (biochemical) and direct
(distortion of the nucleus) mechanotransductive events are covered later in this chapter.
Both forms, at the nuclear level, will lead to different genes being transcribed in response
to the changing mechanical environment, resulting in differential protein expression
typical of different phenotypes, for example, osteocalcin and osteopontin in bone-cell
differentiation [64, 66].
Focal Adhesion Complexes
Without adhesion, tissue cells die through apoptotic mechanisms known as anoikiseven
quicker than through lack of nutrients [68]. Attachment of cells to the surfaces is dependent
to several factors: cell-surface proteins, such as integrins, cadherins, selectins, and immu-
noglobulins, to ECM characteristics, such as type and concentration of matrix proteins, to
matrix stiffness and physical characteristics of the matrix [69]. Integrins are considered
the most important cell-surface proteins in cell/interfacial research as they form the base
of FA complexes (Figure 12.1) [70]. They are a heterodimer consisting of an α and a β sub-
unit, each with three domains: an extracellular domain in contact with ECM, a transmem-
brane, and a cytoplasmic domain. Currently, about 18 varieties of α subunits and eight of
β subunits and twenty-four separate combinations are known. It seems integrins are major
transmitters of biomechanical signals from the ECM to the cell interior. The process
