Cell Migration in Engineered Microstructured Surfaces - Innovative Approaches to Cell Biomechanics - page 146

Fig. 10.6 , all cells observed would turn at the boundary with the narrow grooves
( w = 0.5, 1 ʼm), independently of the angle of approach. In contrast, for wider grooves
( w = 3, 4, 5 ʼm), cells with a higher angle of approach tend to cross the boundary,
whereas cells with a lower angle of approach tend to turn at the boundary.

10.5.2 Performance of Migrating Cell Filtering

by Microgrooved Surface

The performance of grooved surfaces as cell filters can be quantified by the Youden
Index and the receiver operating characteristic (ROC) curves that have been fre-
quently applied for two-class prediction problem in the investigation of the perfor-
mance of clinical tests (Zweig and Campbell 1993 ). The Youden Index in this assay
is defined as:

{ }

(10.1)

J = max q P qq ≤ repel − P qq ≤ attract

th th

th

where P [ θ ≤ θ th |repel] is the conditional probability for θ ≤ θ th , given that the cells
are repelled, and P [ θ ≤ θ th |attract] is the conditional probability for θ ≤ θ th , given that
the cells are attracted. In determining an optimal threshold angle of approach for
cell repulsion/attraction by the grooved surface, P [ θ ≤ θ th |repel] and P [ θ ≤ θ th |attract]
are respectively the true positive rate and the false positive rate, and J is proportional
to the maximum probability of getting a correct answer. The critical threshold value
θ th , which achieves this maximum J , is defined as the threshold angle of approach of
the cell repelled by the grooved surface. The probability P [ θ ≤ θ th |repel] is plotted as
a function of the probability P [ θ ≤ θ th |attract] to give the ROC curves. The area
under the ROC curve (AUC) is used as a measure of the performance of the cell
filtering process with an intersecting grooved surface. An AUC > 0.9 indicates high
accuracy, while 0.7-0.9, 0.5-0.7, and 0.5 respectively indicate moderate accuracy,
low accuracy, and a chance result (Akobeng 2007 ).
Based on the Youden Index in Eq. ( 10.1 ), the threshold angles, θ th , are estimated
to be 54.5, 43.5, and 53 for the grooves of w = 3, 4, and 5 ʼm, respectively. The
values of AUC are 1.00, 1.00, and 0.86 for w = 3, 4, and 5 ʼm, respectively. The
result suggested that a moderate discrimination of the angle of approach is realized
by the intersecting grooves ( w = 5 ʼm, s = 5 ʼm). Furthermore, the intersecting
grooves ( w = 3 and 4 ʼm, s = 5 ʼm) enables discrimination of cell angle of approach
with high accuracy by repelling cells with lower angle of approach than the thresh-
old of 54.5 ( w = 3 ʼm) and 43.5 ( w = 4 ʼm).

10.5.3 Effect of Groove Width on Cell Migration

Cell orientation and alignment along the longer axis of the parallel multiple
grooves is known to increase with decreasing groove width or spacing (Lim and
Donahue 2007 ). To examine the discrimination property of the narrower grooves,