Biology subjects

Frieboes, H. B.

Publications and source records attributed to Frieboes, H. B..

4 recordsLinked to original sources

bioRxiv2024

Drug-loaded nanoparticles for cancer therapy: a high-throughput multicellular agent-based modeling study

Interactions between biological systems and engineered nanomaterials have become an important area of study due to the application of nanomaterials in medicine. In particular, the application of nanomaterials for cancer diagnosis or treatment presents a challenging opportunity due to the complex biology of this disease spanning multiple time and spatial scales. A system-level analysis would benefit from mathematical modeling and computational simulation to explore the interactions between anticancer drug-loaded nanoparticles (NPs), cells, and tissues, and the associated parameters driving this system and a patients overall response. Although a number of models have explored these interactions in the past, few have focused on simulating individual cell-NP interactions. This study develops a multicellular agent-based model of cancer nanotherapy that simulates NP internalization, drug release within the cell cytoplasm, "inheritance" of NPs by daughter cells at cell division, cell pharmacodynamic response to the intracellular drug, and overall drug effect on tumor dynamics. A large-scale parallel computational framework is used to investigate the impact of pharmacokinetic design parameters (NP internalization rate, NP decay rate, anticancer drug release rate) and therapeutic strategies (NP doses and injection frequency) on the tumor dynamics. In particular, through the exploration of NP "inheritance" at cell division, the results indicate that cancer treatment may be improved when NPs are inherited at cell division for cytotoxic chemotherapy. Moreover, smaller dosage of cytostatic chemotherapy may also improve inhibition of tumor growth when cell division is not completely inhibited. This work suggests that slow delivery by "heritable" NPs can drive new dimensions of nanotherapy design for more sustained therapeutic response.

systems biology↗

bioRxiv2020

Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

Colorectal cancer (CRC) and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic (PVE) model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could "reawaken" after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.

systems biology↗

bioRxiv2016

MultiCellDS: a standard and a community for sharing multicellular data

Cell biology is increasingly focused on cellular heterogeneity and multicellular systems. To make the fullest use of experimental, clinical, and computational efforts, we need standardized data formats, community-curated \"public data libraries\", and tools to combine and analyze shared data. To address these needs, our multidisciplinary community created MultiCellDS (MultiCellular Data Standard): an extensible standard, a library of digital cell lines and tissue snapshots, and support software. With the help of experimentalists, clinicians, modelers, and data and library scientists, we can grow this seed into a community-owned ecosystem of shared data and tools, to the benefit of basic science, engineering, and human health.

systems biology↗

bioRxiv2016

MultiCellDS: a community-developed standard for curating microenvironment-dependent multicellular data

Exchanging and understanding scientific data and their context represents a significant barrier to advancing research, especially with respect to information siloing. Maintaining information provenance and providing data curation and quality control help overcome common concerns and barriers to the effective sharing of scientific data. To address these problems in and the unique challenges of multicellular systems, we assembled a panel composed of investigators from several disciplines to create the MultiCellular Data Standard (MultiCellDS) with a use-case driven development process. The standard includes (1) digital cell lines, which are analogous to traditional biological cell lines, to record metadata, cellular microenvironment, and cellular phenotype variables of a biological cell line, (2) digital snapshots to consistently record simulation, experimental, and clinical data for multicellular systems, and (3) collections that can logically group digital cell lines and snapshots. We have created a MultiCellular DataBase (MultiCellDB) to store digital snapshots and the 200+ digital cell lines we have generated. MultiCellDS, by having a fixed standard, enables discoverability, extensibility, maintainability, searchability, and sustainability of data, creating biological applicability and clinical utility that permits us to identify upcoming challenges to uplift biology and strategies and therapies for improving human health.

systems biology↗