Passive nuclear transport deviates from Fickian behavior in prostate and breast cell types

Sep 22, 2026

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Nuclear trafficking is essential for cellular function and enables nucleustargeted drug delivery, yet passive nuclear transport variation across cell types and phenotypic states remains poorly resolved. The study measures passive uptake of fluorescent molecular cargoes spanning 500–20,000 Da across multiple cell lines. Results show cell-line-specific nuclear restrictions, with uptake lacking a monotonic dependence on molecular weight, consistent with non-Fickian transport. Transforming a healthy breast model into an invasive-like phenotype via TGF-Beta shifts passive nuclear transport toward that of an established invasive cancer line, linking phenotype to altered nuclear permeability and cancer biophysics.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Passive nuclear transport and NPC-mediated diffusion

Size thresholds, active transport, and non-Fickian entry

Cell-cycle/state dependence and disease relevance

Study design across epithelial cell lines

RESEARCH ARTICLE Passive nuclear transport deviates from Fickian behavior in prostate and breast cell types Nicholas R. Scotta, Alexander J. Linb, Brian Belardib, and Sapun H. Parekha aDepartment of Biomedical Engineering, University of Texas at Austin, Austin, TX, USA; bMcKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX, USA ABSTRACT Nuclear trafficking is essential for cellular function and biomedical applications such as nucleustargeted drug delivery; however, how passive nuclear transport varies across cell types and phenotypic states remains poorly understood. Here, we investigate passive nuclear transport of fluorescent molecular cargoes spanning 500–20,000 Da across multiple cell lines. We observe cell-line-specific nuclear restrictions and find that passive nuclear uptake does not exhibit a monotonic dependence on molecular weight, suggesting non-Fickian transport behavior. Furthermore, transforming a healthy breast cell model into an invasive-like phenotype via TGF-Beta treatment significantly altered passive nuclear transport characteristics, closely resembling those of a well-established invasive breast cancer cell line. These phenotype-dependent changes in nuclear permeability provide new insight into fundamental biophysical alterations associated with cancerous cellular transformation. ARTICLE HISTORY Received 22 September 2025 Revised 12 January 2026 Accepted 16 January 2026 KEYWORDS Cancer; nuclear trafficking; size-dependent transport; nuclear transport; membrane diffusion; transport in cancer CONTACT Nicholas R. Scott [nrscott@utexas.edu](nrscott@utexas.edu); Sapun H. Parekh sparekh@utexas.edu Department of Biomedical Engineering, University of Texas at Austin, 107 W. Dean Keeton St., Austin, TX 78712, USA Supplemental data for this article can be accessed online at [https://doi.org/10.1080/19491034.2026.2620223](https://doi.org/10.1080/19491034.2026.2620223) © 2026 The Author(s) . Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. 2 N. R. SCOTT ET AL. Introduction Passive nuclear transport is integral for small molecules and proteins that maintain normal cell behaviors. By traveling through nuclear pore complexes (NPCs) to traverse the double bilayer nuclear envelope, such cargo undergoes nucleo-cytoplasmic transport. While very small, minimally polar, or nonpolar molecules may traverse the nuclear envelope directly, without the use of the NPC [ 1], most transport occurs via the NPCs [2]. Passive diffusive transport into or out of the nucleus has been assumed to essentially obey Fickian diffusion up until a soft cutoff, where larger cargo (that above the cutoff) passive transport across the NPC becomes inefficient [2,3]. Instead, larger molecules (greater than , 40 kDa), typically require nuclear transport receptors, such as importin-β or other karyopherins, to attach to the cargo’s nuclear localization sequence (NLS) to facilitate active transport into the nucleus [4]. However, certain large molecules possess specific molecular properties that allow them to passively enter the nucleus through the NPC without an NLS [5,6], in contrast to the majority of larger molecules, which exhibit minimal passive transport–highlighting the complexity of passive nuclear entry. Further complicating the picture of passive transport is that different cells may exhibit different nuclear transport properties for reasons such as cell cycle or cell state. For example, ear

FAQs

What is the central finding about passive nuclear transport across different cell lines?

Passive nuclear uptake is cell-line specific and does not show a monotonic dependence on molecular weight, indicating non-Fickian transport behavior.

How do the authors test how cargo size affects nuclear entry?

They investigate passive diffusion of fluorescent molecular cargoes across a molecular weight range of 500–20,000 Da using multiple cell lines.

How does inducing an invasive-like breast cell phenotype change passive nuclear transport?

TGF-Beta treatment alters passive nuclear transport characteristics, producing changes closely resembling those of a well-established invasive breast cancer cell line.

Sep 22, 2026

Upload by Patrick