title: Cell-structure specific necrosis by optical-trap induced intracellular nuclear oscillation.
abstract: A drug-free procedure for killing malignant cells in a cell-type specific manner would represent a significant breakthrough for leukemia treatment. Here, we show that mechanically vibrating a cell in a specific oscillation condition can significantly promote necrosis. Specifically, oscillating the cell by a low-power laser trap at specific frequencies of a few Hz was found to result in increased death rate of 50% or above in different types of myelogenous leukemia cells, while normal leukocytes showed very little response to similar laser manipulations. The alteration of cell membrane permeability and cell volume, detected from ethidium bromide staining and measurement of intracellular sodium ion concentration, together with the observed membrane blebbing within 10min, suggest cell necrosis. Mechanics modelling reveals severe distortion of the cytoskeleton cortex at frequencies in the same range for peaked cell death. The disruption of cell membrane leading to cell death is therefore due to the cortex distortion, and the frequency at which this becomes significant is cell-type specific. Our findings lay down a new concept for treating leukemia based on vibration induced disruption of membrane in targeted malignant cells.
authors.affiliation: Department of Mechanical Engineering, University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
authors.forename: X X
authors.initials: XX
authors.lastname: Sun
authors.affiliation: Department of Mechanical Engineering, University of Hong Kong, Pokfulam Road, Hong Kong, PR China. Electronic address: zhouzhuolong@gmail.com.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Zhou
authors.affiliation: Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
authors.forename: C H
authors.initials: CH
authors.lastname: Man
authors.affiliation: Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
authors.forename: A Y H
authors.initials: AYH
authors.lastname: Leung
authors.affiliation: Department of Mechanical Engineering, University of Hong Kong, Pokfulam Road, Hong Kong, PR China.
authors.forename: A H W
authors.initials: AHW
authors.lastname: Ngan
mesh_terms: D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000473:pathology*; D048429:Cell Size; D003593:Cytoplasm; D003599:Cytoskeleton / Q000473:pathology*; D006801:Humans; D007951:Leukemia, Myeloid; D052898:Optical Tweezers; D014732:Vibration
keywords: Frequency; Leukemia; Mechanical force; Necrotic cell death; Optical trap