Alice Lam

All Publications

• Plasma membrane folding enables constant surface area-to-volume ratio in growing mammalian cells. Current biology : CB Wu, W., Lam, A. R., Suarez, K., Smith, G. N., Duquette, S. M., Yu, J., Mankus, D., Bisher, M., Lytton-Jean, A., Manalis, S. R., Miettinen, T. P. 2025; 35 (7): 1601-1611.e5

  Abstract

  All cells are subject to geometric constraints, including the surface area-to-volume (SA/V) ratio, which can limit nutrient uptake, maximum cell size, and cell shape changes. Like the SA/V ratio of a sphere, it is generally assumed that the SA/V ratio of cells decreases as cell size increases. However, the structural complexity of the plasma membrane makes studies of the surface area challenging in cells that lack a cell wall. Here, we investigate near-spherical mammalian cells using single-cell measurements of cell mass and plasma membrane proteins and lipids, which allow us to examine the cell size scaling of cell surface components as a proxy for the SA/V ratio. Surprisingly, in various proliferating cell lines, cell surface components scale proportionally with cell size, indicating a nearly constant SA/V ratio as cells grow larger. This behavior is largely independent of the cell-cycle stage and is also observed in quiescent cells, including primary human monocytes. Moreover, the constant SA/V ratio persists when cell size increases excessively during polyploidization. This is enabled by increased plasma membrane folding in larger cells, as verified by electron microscopy. We also observe that specific cell surface proteins and cholesterol can deviate from the proportional size scaling. Overall, maintaining a constant SA/V ratio ensures sufficient plasma membrane area for critical functions such as cell division, nutrient uptake, growth, and deformation across a wide range of cell sizes.

  View details for DOI 10.1016/j.cub.2025.02.051

  View details for PubMedID 40101718

  View details for PubMedCentralID PMC11981834

• Triple negative breast cancer cells acquire lymphocyte proteins and genomic DNA during trogocytosis with T cells. PeerJ Sivakoses, A., Marcarian, H. Q., Arias, A. M., Lam, A. R., Ihedioha, O. C., Santamaria-Barria, J. A., Gurtner, G. C., Bothwell, A. L. 2025; 13: e19236

  Abstract

  Trogocytosis is the process by which a recipient cell siphons small membrane fragments and proteins from a donor cell and can be utilized by cancer cells to avoid immune detection. We observed lymphocyte specific protein expressed by triple negative breast cancer (TNBC) cells via immunofluorescence imaging of patient samples. Image analysis of Cluster of Differentiation 45RA (CD45RA) expression, a naïve T cell specific protein, revealed that all stages of TNBCs express CD45RA. Flow cytometry revealed TNBC cells trogocytose CD45 protein from T cells. We also showed that the acquisition of these lymphoid markers is contact dependent. Confocal and super-resolution imaging further revealed CD45+ spherical structures containing T cell genomic DNA inside TNBC cells after co-culture. Trogocytosis between T cells and TNBC cells altered tumor cell expression of PTPRC, the gene that encodes for CD45. Our results revealed that CD45 is obtained by TNBC cells from T cells via trogocytosis and that TNBC cells express CD45 intracellularly and on the membrane.

  View details for DOI 10.7717/peerj.19236

  View details for PubMedID 40183054

  View details for PubMedCentralID PMC11967428

• Cell- intrinsic mechanical regulation of plasma membrane accumulation at the cytokinetic furrow PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Alonso-Matilla, R., Lam, A. R., Miettinen, T. P. 2024; 121 (29): e2320769121

  Abstract

  Cytokinesis is the process where the mother cell's cytoplasm separates into daughter cells. This is driven by an actomyosin contractile ring that produces cortical contractility and drives cleavage furrow ingression, resulting in the formation of a thin intercellular bridge. While cytoskeletal reorganization during cytokinesis has been extensively studied, less is known about the spatiotemporal dynamics of the plasma membrane. Here, we image and model plasma membrane lipid and protein dynamics on the cell surface during leukemia cell cytokinesis. We reveal an extensive accumulation and folding of the plasma membrane at the cleavage furrow and the intercellular bridge, accompanied by a depletion and unfolding of the plasma membrane at the cell poles. These membrane dynamics are caused by two actomyosin-driven biophysical mechanisms: the radial constriction of the cleavage furrow causes local compression of the apparent cell surface area and accumulation of the plasma membrane at the furrow, while actomyosin cortical flows drag the plasma membrane toward the cell division plane as the furrow ingresses. The magnitude of these effects depends on the plasma membrane fluidity, cortex adhesion, and cortical contractility. Overall, our work reveals cell-intrinsic mechanical regulation of plasma membrane accumulation at the cleavage furrow that is likely to generate localized differences in membrane tension across the cytokinetic cell. This may locally alter endocytosis, exocytosis, and mechanotransduction, while also serving as a self-protecting mechanism against cytokinesis failures that arise from high membrane tension at the intercellular bridge.

  View details for DOI 10.1073/pnas.2320769121

  View details for Web of Science ID 001279325400001

  View details for PubMedID 38990949

  View details for PubMedCentralID PMC11260091

• Single-cell monitoring of dry mass and dry mass density reveals exocytosis of cellular dry contents in mitosis. eLife Miettinen, T. P., Ly, K. S., Lam, A., Manalis, S. R. 2022; 11

  Abstract

  Cell mass and composition change with cell cycle progression. Our previous work characterized buoyant mass dynamics in mitosis (Miettinen et al., 2019), but how dry mass and cell composition change in mitosis has remained unclear. To better understand mitotic cell growth and compositional changes, we develop a single-cell approach for monitoring dry mass and the density of that dry mass every ~75 s with 1.3% and 0.3% measurement precision, respectively. We find that suspension grown mammalian cells lose dry mass and increase dry mass density following mitotic entry. These changes display large, non-genetic cell-to-cell variability, and the changes are reversed at metaphase-anaphase transition, after which dry mass continues accumulating. The change in dry mass density causes buoyant and dry mass to differ specifically in early mitosis, thus reconciling existing literature on mitotic cell growth. Mechanistically, cells in early mitosis increase lysosomal exocytosis, and inhibition of lysosomal exocytosis decreases the dry mass loss and dry mass density increase in mitosis. Overall, our work provides a new approach for monitoring single-cell dry mass and dry mass density, and reveals that mitosis is coupled to extensive exocytosis-mediated secretion of cellular contents.

  View details for DOI 10.7554/eLife.76664

  View details for PubMedID 35535854

  View details for PubMedCentralID PMC9090323