Macro-scale phenomena of arterial coupled cells: a massively parallel simulation

Area of Science:

• Computational biology
• Cardiovascular physiology
• Biophysics

Background:

• Impaired mass transfer of vasoactive substances in arterial bifurcations is linked to atherosclerosis.
• Arterial endothelial cells (ECs) and smooth muscle cells (SMCs) exhibit differential responses to hemodynamics and communicate to coordinate macro-scale responses.
• Understanding intercellular communication mechanisms is vital for elucidating atherosclerotic lesion development.

Purpose of the Study:

• To investigate the response of coupled ECs and SMCs to spatial gradients of blood-borne agonists.
• To determine the effect of micro-scale intercellular coupling on macro-scale arterial responses.
• To analyze the role of homocellular and heterocellular calcium (Ca2+) coupling in signal propagation and arterial function.

Main Methods:

• Development of a computational model of an arterial segment with large populations of coupled ECs and SMCs.
• Simulation of four cases altering homocellular and heterocellular intercellular coupling under identical agonist concentration gradients.
• Utilizing massively parallel computational architectures (Blue Gene) to solve hundreds of thousands of coupled nonlinear ordinary differential equations.

Main Results:

• Heterocellular Ca2+ coupling between ECs and SMCs is critical for rapid arterial segment response to agonist gradients.
• In the absence of heterocellular coupling, homocellular Ca2+ coupling among SMCs is essential for axial propagation of Ca2+ waves.
• Desynchronized intracellular Ca2+ oscillations in coupled SMCs are necessary for signal propagation; decoupling heterocellular potential removes ECs' inhibitory effect on SMC Ca2+ dynamics.

Conclusions:

• Intercellular communication, particularly heterocellular coupling, plays a significant role in the dynamic response of arterial segments to vasoactive stimuli.
• The study highlights the importance of specific coupling mechanisms (heterocellular vs. homocellular) in signal propagation and regulation of vascular cell function.
• Massively parallel computation enables the study of macro-scale phenomena driven by micro-scale cellular interactions, advancing our understanding of vascular diseases like atherosclerosis.