Search bioRxiv⌕ Search

bioRxiv · 10.64898/2026.07.12.738114

Quantitative Comparison of 3D-1D Vascular Coupling Models: Lateral Average versus Sphere of Influence Methods

Abstract

Computational models coupling one-dimensional vascular networks with three-dimensional tissue domains are widely used for predicting blood flow distribution in tumor perfusion, drug delivery, and therapeutic planning. Two prominent coupling paradigms have emerged: the Lateral Average Model (LAM) which implements distributed transmural exchange via a vessel wall conductivity parameter{gamma} (m Pa-1 s-1), and the Sphere of Influence (SOI) model, which employs localized terminal coupling via a source sphere radius{varepsilon} (m). Despite their broad application, systematic quantitative comparisons of their parametric behavior and predictive equivalence remain lacking. We compare LAM and SOI in 3D-1D simulations on a benchmark vascular network and a porcine liver study with a hepatic arterial network reconstructed from CT arteriography. Across a benchmark vascular network under three sink configurations, the LAM net flow rate rose smoothly with{gamma} and saturated at a plateau, while the SOI net flow rate increased with{varepsilon} without saturating; as a result, global-flow equivalence between the two formulations exists only for particular boundary geometries, and not at all within the tested parameter range for one of the three configurations examined. Despite this partial agreement in total flow, the two models diverged substantially in regional perfusion: in a porcine hepatic arterial network reconstructed from CT arteriography, SOI predicted stable perfusion fractions to two regions of interest across its full tested parameter range, whereas LAM predictions for the same regions varied several-fold with vessel wall permeability and, at low permeability, could invert which region received more flow. These results indicate that the choice of coupling model has limited consequence for predicted total organ flow but substantial consequence for predicted local drug delivery, and we provide guidance for selecting between the two formulations depending on the clinical or research question being asked. Author SummaryWhen doctors plan treatments for liver cancer, they often rely on computer simulations to predict how blood flows through the liver and how well a drug will reach the tumor. These simulations depend on mathematical models that describe how blood moves from vessels into surrounding tissue. Two commonly used approaches exist for building these models, but researchers have generally chosen between them based on habit or convenience rather than on a principled understanding of how their predictions differ. In this work, we directly compared these two approaches, one that spreads blood exchange continuously along the vessel wall, and one that delivers blood from the vessel tips into a surrounding spherical zone, using both a simple test network and a realistic pig liver reconstructed from medical imaging. We found that the two approaches can agree on the total amount of blood reaching the liver, but disagree substantially on where that blood goes within the tissue. This distinction matters enormously for treatment planning: a model that predicts the right total blood flow but delivers it to the wrong region of the liver could lead to an inaccurate forecast of drug concentration at the tumor site. Our results provide practical guidance for researchers on which approach to use depending on what information is available and what question is being asked.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Amare, R., Vargun, D., Zhang, P., Parrish, S., Stolley, D., Santos, C., Jacobsen, M., Cressman, E., Riviere, B., Fuentes, D.. 2026-07-17. Quantitative Comparison of 3D-1D Vascular Coupling Models: Lateral Average versus Sphere of Influence Methods. https://doi.org/10.64898/2026.07.12.738114

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A quantum state of mitochondria in the living cell

The high energy-efficiency of life is hard to understand only with classical physics. Many efforts have been made to study its mechanism based on quantum mechanics; the progress is nevertheless slow due to lack of experimental evidence with living cells. Here, combining experiments on cells, tissues and mitochondria with a theoretical model, we demonstrate a quantum state of mitochondria, which can be employed to modulate ATP production in living cells. We found an anomalous 71.0-THz oscillation mode only in living cells and tissues, which is highly determined by intact structure of mitochondria, and cannot be assigned to any specific molecules. Based on experimental data, a quantum model of light-matter coupling was introduced to trace the origin of this mode. Our calculations suggest a quantum superposition state of functional mitochondrion that forms by the coupling of light and lipid CH2 bonds in functional cristae, and induces a splitting of the intrinsic CH2 vibration mode of 87 THz to two levels at 71 THz and 103 THz, respectively. The former can be observed only in living cells and tissues; whereas the latter falls in the range (90-110 THz) of biomolecular and water vibrations, thus indistinguishable. Additional experiments revealed this mitochondrial quantum state able to serve as an efficient channel to modulate ATP production. Our findings provide a quantum mechanics view for understanding living cells, and it will be interesting to further explore whether such quantum state could act as a channel for energy metabolism, and even information transmission in life.

biophysics↗

Mechanistical and structural basis of Kv channel inhibition by 4 aminopyridine

Inhibition of Kv channels by 4-aminopyridine (4AP) improves motor function in multiple sclerosis by enhancing neuronal excitability. The mechanism of inhibition and the structural basis of 4AP binding to Kv channels remain unclear. Here, we determined the structure of the Shaker V369I-I372L-S376T (ILT) mutant bound to 4AP at 3.3 [A], demonstrating that 4AP binds to the closed state of the channel. This structure is inconsistent with an open channel block mechanism. Electrophysiology experiments show that 4AP binds even when intracellular pore access is constitutively blocked, suggesting that 4AP enters the pore through membrane-facing fenestrations. MD simulations and mutational analysis agree with the proposed fenestration pathway and suggest that 4AP binds in its neutral form. These results support a mechanism where 4AP binds to a partially activated closed state that prevents complete activation of Kv channels, explaining its pharmacological activity.

biophysics↗

Substrate binding reorganizes the energetic landscape of Plasmodium falciparum hexose transporter PfHT1

Malaria parasites depend on the Plasmodium falciparum hexose transporter PfHT1 for sugar uptake, yet how substrate binding reshapes transporter energetics and kinetics of sugar transport remains poorly understood. Here, we investigate how glucose reorganizes the conformational landscape, transition pathways, and residue interaction network underlying membrane transport. Using over 800 s of adaptive molecular dynamics simulations combined with Markov state models, transition-path theory, residue-contact analysis, and graph attention learning, we reconstruct the apo and glucose-bound conformational cycles. We show that glucose selectively stabilizes productive outward-facing, occluded, and inward-facing conformations, reshapes transition kinetics, and channels reactive flux through the occluded state. We identify TM7b helix cracking as a local structural transition coupled to extracellular-gate closure and substrate progression, providing a flexible connection between the binding pocket and global alternating access. Experimental testing of mechanistically critical residues validated their functional importance in PfHT1-dependent sugar utilization. Together, these results show how substrate binding reorganizes the energetic, kinetic, and interaction landscape of membrane transport and establish a transferable framework for studying transporter mechanisms.

biophysics↗