Modeling and Simulation of Osteocyte-Fluid Interaction in a Lacuno-Canalicular Network in Three Dimensions

Abstract

Bone health relies on its cells' ability to sense and respond to mechanical forces, a process primarily managed by osteocytes embedded within the bone matrix. The cells reside in the lacuno-canalicular network (LCN), a complex structure, comprised of lacunae (small cavities) and canaliculi (microscopic channels), through which they communicate and receive nutrients. The mechanotransduction (MT) process, by which osteocytes convert mechanical signals from mechanical loading into biochemical responses, is essential for bone remodeling but remains poorly understood. Both in-vitro and in-vivo studies present challenges in directly measuring the cellular stresses and strains involved, making computational modeling a valuable tool for studying osteocyte mechanics. In this dissertation, we present a coarse-grained, integrative model designed to simulate stress and strain distributions within an osteocyte and its microenvironment. Our model features the osteocyte membrane represented as a network of viscoelastic springs, with six slender, arm-like osteocytic processes extending from the membrane. The osteocyte is immersed in interstitial fluid and encompassed by the rigid extracellular matrix (ECM). The cytosol and interstitial fluid are both modeled as water-like, viscous incompressible fluids, allowing us to capture the fluid-structure interactions crucial to understanding the MT. To simulate these interactions, we employ the Lattice Boltzmann - Immersed Boundary (LB-IB) method. This approach couples the Lattice Boltzmann method, which numerically solves fluid equations, with the immersed boundary method, which handles the interactions between the osteocyte structures and the surrounding fluids. This framework consists of a system of integro-partial differential equations describing both fluid and solid dynamics, enabling a detailed examination of force, strain, and stress distribution within the osteocyte. Major results include 1) increased incoming flow routes results in increased stress and strain, 2) regions of higher stress and strain are concentrated near the junctions where the osteocytic processes meet the main body.