Simulation Based Analysis of Nanocarrier Internalization: Exciting Challenges with a New Computational Tool - Intracellular Delivery: Fundamentals and Applications - page 126

Direct Computer Mapping (DCM) seems to be an effective tool for the organization
of these collaborations.
Looking at the Chapters of this Volume it is obvious that the majority of the con-
tributions have very sophisticated and deep experimental background, related to vari-
ous specific details. From an engineering point of views, they are well-elaborated
pieces of a puzzle. However, our simplified, but systematic computational model
emphasizes the hypothetical big picture. Similarly to bridge building, in computa-
tional systems biology we have to construct the bridge from both sides and, hope-
fully, to meet in the middle.

Keywords Endocytosis • Exocytosis • Internalization and trafficking • Direct Computer
Mapping • Biosystem process modeling • Simulation tool

Abbreviations

NV nanovehicle

L ligand, making possible the association of the drug with nanovehicle

D drug (or gene)

R receptor

Lip lipid, supporting the specific transport through the lipid raft

Targ target component in the cytoplasm

Degr fictitious terminating component for the degradation of NV, L, R and D

containing components

Mot motor proteins, contributing to the exocytosis of nanovehicles and of the

drug

FPM fluid phase macropinocytosis

RME receptor-mediated endocytosis

NAE nonspecific adsorptive endocytosis

LRME lipid-rafts mediated endocytosis

DCM Direct Computer Mapping

R1-R40 elementary reactions

1 Overview of the Problem to be Modeled

The cellular uptake of extracellular ligands, soluble molecules, proteins and lipids
from the extracellular surface occurs by endocytosis, a process where localized
regions of the plasma membrane invaginate and pinch off to form endocytic vesi-
cles. Many of the endocytosed molecules and particles travel through the lyso-
somes and degrade. Endocytosis occurs both constitutively or in a triggered
response to extracellular signals. Many cell types undergo endocytosis continu-
ously where a large fraction of the plasma membrane is internalized every hour.