HETEROGENEOUS NANOSTRUCTURES FOR BIOMEDICAL DIAGNOSTICS - Bio-Inspired and Nanoscale Integrated Computing - page 436

therapeutic applications. The MEMS and NEMS sensors offer an entry point to
address biomedical issues. Their special and temporal resolution provides a basis
to tackle the micro- and nanoscale domains otherwise difficult with the conven-
tional technology.
In clinical medicine, coronary artery disease or atherosclerosis remains the
leading cause of death in the industrialized nations. Atherosclerosis involves
complex plaque formation in the arterial vessels and is considered to be an
inflammatory disease [15]. Oxidized low-density lipoprotein cholesterol (oxLDL)
has been considered important in the development of these inflammatory
processes with the seminal observations that LDL must be oxidatively modified
for it to be taken up by the inflammatory cells that are present in the blood and
tissues [16] (Fig. 16.7). In this context, the development of nanowire sensors
provides a new avenue to understand the fundamentals of oxidative modification
of LDL in the arterial circulation with unprecedented sensitivity and selectivity.
Biomechanical forces, especially fluid and solid shear stresses, have significant
effects on the arterial wall [17-19]. Fluid shear stress, the tangential drag force of
blood passing along the surface of the endothelium [20], has metabolic as well as
mechanical effects on endothelial cell (EC) function [21-23]. At the arterial
bifurcations or branching points, endothelial cells become hyperpermeable in
the presence of hyperlipoproteinemia that may favor intimal uptake and retention
of LDL, resulting in local oxidative degradation of trapped LDL [24-26]. A
complex flow profile develops at bifurcations, namely, flow separation and
migrating stagnation points that create low and oscillating shear stress (Fig. 16.8).
At the lateral walls of arterial bifurcations, disturbed flow, including oscilla-
tory flow (bidirectional with no net forward flow), is considered to be an inducer
of oxidative stress that favors the pathogenesis of atherosclerotic plaque, whereas
in the medial wall of bifurcation, pulsatile flow develops and down-regulates
adhesion molecules,

inflammatory cytokines, and oxidative stress [27, 28]

Cholesteryl ester

Phospholipid

Triglyceride

Unesterified
cholesterol

ApoB-100

Figure 16.7. A three-dimensional representation of low density lipoprotein cho-
lesterol (LDL). LDL particle contains phospholipids with their hydrophobic tails
exposed to the outer surface. Embedded by these phospholipids are cholesteryl
ester, and triglyceride and unesterified cholesterol. Surrounded the phospho-
lipids are ApoB-100 protein. A typical LDL particle has a typical diameter from 25
to 27 nm.