Determination of Order in Desmosomes and Resolution of Mechanisms of Pemphigus Vulgaris Open Access

Raju, Siddharth Shankar (2016)

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Desmosomes are dynamic, adhesive, intercellular junctions that provide mechanical stability for skin. This stability is undermined by the autoimmune disorder Pemphigus Vulgaris (PV). Previous work has found evidence to suggest that PV interferes with desmosomal adhesion and in this manner undermines mechanical stability of skin. We hypothesize that healthy skin contains "ordered" desmosomes while diseased skin contains "disordered" desmosomes, and that the main mechanism of PV is to destroy the structure of ordinarily ordered junctions which provide the strongest possible adhesion. To this end we have developed mathematical models to understand the dynamics of the desmosome system and analyzed the subsequent simulated data to investigate how order may arise.

Table of Contents

1 Introduction. 1

1.1 Biological Background. 1

1.2 Hypothesis and Method Background. 4

2 Modeling. 9

2.1 Spatial Analysis. 9

2.2 Intensity Function. 12

2.3 Derivations. 15

2.3.1 Derivation of Intensity Function for a Single Protein. 15

2.3.2 Derivation of Intensity Function for Multiple Proteins. 16

2.4 Preliminary Observations and Method Development. 17

2.5 Alternative Formulation. 25

3 Experiment. 28

3.1 Apparatus. 28

3.2 Data Extraction. 30

3.3 Final Analysis. 31

3.4 Preliminary Data. 31

4 Conclusion. 33

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